Table 1.
Rationale for “causal" or "likely causal" diagnostic interpretation by multidisciplinary research team in individuals with variants that could not be given an ACMG classification or that were classified as ACMG VUS
| CAUSES ID no. | Sex | Gene | Variant | Mechanism | Disease | ACMG variant classification | Diagnostic interpretation by multidisciplinary research team | Rationale for diagnostic interpretation |
|---|---|---|---|---|---|---|---|---|
| G001-1 | F | ASXL3 | NP_085135.1:p.Asn1224Ter | de novo heterozygous | Bainbridge-Ropers syndrome | VUS | definitely causal | phenotype consistent with Bainbridge-Ropers syndrome; bioinformatics predict that variant is damaging |
| G004-1 | F | TBCK | NP_001156907.2:p.Arg261Ser | compound heterozygous | infantile hypotonia with psychomotor retardation and characteristic facies 3 | likely pathogenic | probably causal | phenotype characteristic of reported cases; VUS predicted as damaging and allelic to likely pathogenic variant |
| NM_001163435.3:c.2060-2A>G | VUS | |||||||
| G005-1 | F | CAMK2G | NP_001354463.1:p.Arg297Trp | de novo heterozygous | mental retardation, autosomal dominant 59 | unclassified | probably causal | phenotype consistent with reported cases; bioinformatics predict that variant is a damaging, missense variant close to that in previously reported cases |
| G010-1 | M | SUZ12 | NP_056170.2:p.Arg654Ter | de novo heterozygous | Imagawa-Matsumoto syndrome | unclassified | probably causal | phenotype consistent with reported cases; bioinformatics predict that variant is damaging |
| G022-1 | M | NRXN1 | NP_001317007.1:p.Ile382Met | de novo heterozygous | affective psychosis with severe obsessive compulsive disorder, onset at about 9 years of age, refractive to treatment; cognitive deterioration | VUS | probably causal | de novo variant predicted to cause haploinsufficiency; very unusual phenotype consistent with that observed in some individuals with NRXN1 haploinsufficiency reported with deletions |
| G025-1 | M | CLTC | NP_004850.1:p.Pro890Leu | de novo heterozygous | mental retardation, autosomal dominant 56 | unclassified | probably causal | phenotype consistent with reported cases; bioinformatics predict that variant is damaging |
| G027-1 | M | SMC1A | NP_006297.2:p.Asp982Val | hemizygous (inherited from mosaic mother) | Cornelia de Lange syndrome 2 | VUS | probably causal | phenotype consistent with Cornelia de Lange syndrome; bioinformatics predict that variant is damaging |
| G035-1 | M | MED12 | NP_005111.2:p.Arg91Leu | hemizygous (maternally inherited) | Ohdo syndrome | VUS | probably causal | phenotype consistent with Ohdo syndrome; similarly affected maternal uncle also carries variant; bioinformatics predict that variant is damaging |
| G036-1 | M | SATB2 | NM_001172509.2:c.474-3C>G | de novo heterozygous | Glass syndrome | VUS | probably causal | phenotype consistent with reported cases; bioinformatics predict that variant alters splicing |
| G044-1 | F | SCN8A | NP_001317189.1:p.Cys324Tyr | de novo heterozygous | early infantile epileptic encephalopathy | VUS | probably causal | phenotype consistent with reported cases; bioinformatics predict that variant is damaging |
| G050-1 | M | EP300 | NP_001420.2:p.Gly2350HisfsTer52 | heterozygous (maternally inherited) | Rubinstein-Taybi syndrome 2 | VUS | definitely causal | phenotype in both proband and mother consistent with Rubinstein-Taybi syndrome; bioinformatics predict that variant is damaging |
| G053-1 | M | KCNQ5 | NP_062816.2:p.Val145Gly | de novo heterozygous | autosomal dominant mental retardation 46 | unclassified | definitely causal | individual included in first published report of "new" genotype-phenotype association |
| G059-1 | M | SLC16A2 | NP_006508.2:p.Arg371Leu | hemizygous (maternally inherited) | Allan-Herndon-Dudley syndrome | VUS | definitely causal | phenotype characteristic of Allan-Herndon-Dudley syndrome |
| G066-1 | M | UBE2A | NP_003327.2:p.Arg95Cys | hemizygous (maternally inherited) | mental retardation, X-linked syndromic, Nascimento type | VUS | probably causal | phenotype in both affected brothers consistent with reported cases; bioinformatics predict that variant is damaging |
| G066-4 | M | UBE2A | NP_003327.2:p.Arg95Cys | hemizygous (maternally inherited) | mental retardation, X-linked syndromic, Nascimento type | VUS | probably causal | phenotype in both affected brothers consistent with reported cases; bioinformatics predict that variant is damaging |
| G070-1 | M | C2orf69 | NP_710156.3:p.Lys282GlnfsTer55 | homozygous | combined oxidative phosphorylation deficiency 53 | VUS | probably causal | phenotype consistent with reported cases; consanguineous family with two early infant deaths in cousins and two additional early childhood deaths in other relatives; bioinformatics predict that variant is damaging |
| G073-1 | M | SOD1 | NP_000445.1:p.Ala124del | homozygous | progressive spastic tetraplegia and axial hypotonia | unclassified | probably causal | very characteristic phenotype consistent with reported cases; similarly affected sib died in childhood; bioinformatics predict that variant is damaging |
| G075-1 | F | MAST1 | NP_055790.1:p.Gly98Val | de novo heterozygous | mega-corpus-callosum syndrome with cerebellar hypoplasia and cortical malformations | unclassified | probably causal | individual included in first published report of "new" genotype-phenotype association |
| G077-1 | F | BPTF | NP_872579.2:p.Arg653Ter | heterozygous (paternally inherited) | neurodevelopmental disorder with dysmorphic facies and distal limb anomalies | unclassified | probably causal | phenotype consistent with reported cases; bioinformatics predict that variant is damaging |
| G089-1 | M | NF1 | NP_001035957.1:p.Gly1190Val | heterozygous (maternally inherited) | neurofibromatosis 1 | VUS | probably causal | phenotype consistent with neurofibromatosis 1; bioinformatics predict that variant is damaging |
| G091-1 | F | TKT | NP_001055.1:p.Arg401His | compound heterozygous | short stature, developmental delay, and congenital heart defects | VUS | definitely causal | phenotype in both sibs consistent with reported cases; bioinformatics predict that both variants are damaging; biochemical assay demonstrates transketolase deficiency |
| NP_001055.1:p.Tyr564del | VUS | |||||||
| G091-4 | M | TKT | NP_001055.1:p.Arg401His | compound heterozygous | short stature, developmental delay, and congenital heart defects | VUS | definitely causal | phenotype in both sibs consistent with reported cases; bioinformatics predict that both variants are damaging; biochemical assay demonstrates transketolase deficiency |
| NP_001055.1:p.Tyr564del | VUS | |||||||
| G092-1 | M | PAK3 | NP_002569.1:p.Ser105Cys | hemizygous (maternally inherited) | mental retardation, X-linked 30/47 | VUS | probably causal | phenotype consistent with reported cases; bioinformatics predict that variant is damaging |
| G103-1 | F | DDX23 | NP_004809.2:p.Arg754Cys | de novo heterozygous | DDX23-related disorder | unclassified | probably causal | phenotype consistent with reported cases; bioinformatics predict that variant is damaging |
| G105-1 | M | SMS | NP_004586.2:p.Met233Ile | hemizygous (maternally inherited) | X-linked mental retardation; Snyder-Robinson type | VUS | definitely causal | phenotype characteristic of Snyder-Robinson syndrome; bioinformatics predict that variant is damaging |
| G107-1 | M | SMARCA2 | NP_003061.3:p.Asp1571GlufsTer46 | de novo heterozygous | Nicolaides-Baraister syndrome | VUS | probably causal | phenotype characteristic of Nicolaides-Baraister syndrome; bioinformatics predict that variant is damaging |
| G114-1 | F | REST | NP_005603.3:p.Gln827Ter | de novo heterozygous | gingival fibromatosis | VUS | probably causal | phenotype characteristic of gingival fibromatosis; variant in last exon, where other variants that cause gingival fibromatosis lie; bioinformatics predict that variant is damaging |
| G117-1 | F | PIGG | NP_001120650.1:p.Asn138Ser | homozygous | autosomal recessive mental retardation 53 | VUS | probably causal | both sibs included in first published report of "new" genotype-phenotype association |
| G117-4 | M | PIGG | NP_001120650.1:p.Asn138Ser | homozygous | autosomal recessive mental retardation 53 | VUS | probably causal | both sibs included in first published report of "new" genotype-phenotype association |
| G122-1 | F | SRCAP | NP_006653.2:p.Val1835ProfsTer13 | de novo heterozygous | non-Floating-Harbor syndrome SRCAP-related neurodevelopmental disability | unclassified | probably causal | phenotype consistent with non-Floating-Harbor syndrome SRCAP-related neurodevelopmental disability; variant lies in exon 25, outside of exons 33–34 involved in Floating-Harbor syndrome; bioinformatics predict that variant is damaging |
| G125-1 | M | ZFYVE26 | NP_056161.2:p.Lys741ArgfsTer3 | compound heterozygous | autosomal recessive spastic paraplegia 15 | likely pathogenic | probably causal | phenotype characteristic of reported cases; compound heterozygote with one likely pathogenic variant and allelic very rare VUS with CADD = 26 |
| NP_056161.2:p.Arg2140Gln | VUS | |||||||
| G134-1 | F | KCNQ2 | NP_742105.1:p.Arg144Trp | de novo heterozygous | early infantile epileptic encephalopathy 7 | unclassified | definitely causal | phenotype consistent with reported cases; bioinformatics predict that variant is damaging |
| G141-1 | F | KMT2C | NP_733751.2:p.Pro4843AlafsTer12 | de novo heterozygous | Kleefstra syndrome 2 | unclassified | probably causal | phenotype consistent with Kleefstra syndrome; bioinformatics predict that variant is damaging |
| G160-1 | M | CIC | NP_001373227.1:p.Ala2056ProfsTer3 | de novo heterozygous | autosomal dominant mental retardation 45 | unclassified | probably causal | phenotype consistent with reported cases; bioinformatics predict that variant is damaging |
| G169-1 | M | HSD17B3 | compound heterozygous | pseudohermaphroditism, male, with gynecomastia | pathogenic | probably causal | phenotype consistent with reported cases; compound heterozygote with one likely pathogenic variant and allelic rare VUS predicted to be damaging | |
| NP_000188.1:p.Ala275Val | VUS | |||||||
| CTLA4 | NP_005205.2:p.Ala54Thr | heterozygous (maternally inherited) | autoimmune lymphoproliferative syndrome, type V | VUS | probably causal | phenotype characteristic of autoimmune lymphoproliferative syndrome; bioinformatics predict that variant is damaging | ||
| G174-1 | M | SET | NP_003002.2:p.Arg44LeufsTer10 | heterozygous (maternally inherited) | autosomal dominant mental retardation 58 | unclassified | probably causal | individual included in first published report of "new" genotype-phenotype association |
| G175-1 | M | ACTB | NP_001092.1:p.Leu110ArgfsTer10 | de novo heterozygous | Baraister-Winter syndrome 1 | VUS | probably causal | phenotype characteristic of Baraister-Winter syndrome; bioinformatics predict that variant is damaging |
| G194-1 | M | MN1 | NP_002421.3:p.Trp1248Ter | de novo heterozygous | CEBALID syndrome | VUS | definitely causal | phenotype characteristic of CEBALID syndrome; bioinformatics predict that variant is damaging |
| G198-1 | M | ARID2 | NC_000012.11:g.46298857_46302229del | de novo heterozygous | Coffin-Siris syndrome 6 | VUS | definitely causal | phenotype consistent with Coffin-Siris syndrome; bioinformatics predict that deletion is damaging |
| G202-1 | M | DLG4 | NP_001308004.1:p.Asn187ThrfsTer3 | de novo heterozygous | intellectual developmental disorder 62 | unclassified | probably causal | phenotype consistent with reported cases; bioinformatics predict that variant is damaging |
| G205-1 | F | NBEA | NP_001371941.1:p.Glu2433ArgfsTer3 | de novo heterozygous | neurodevelopmental disorder with or without early-onset generalized epilepsy | unclassified | probably causal | individual included in first published report of "new" genotype-phenotype association |
| G216-1 | F | COL12A1 | NM_004370.6:c.8319+1G>T | heterozygous (maternally inherited) | Bethlem myopathy | VUS | probably causal | phenotype consistent with Bethlem myopathy; bioinformatics predict that deletion is damaging; variant segregates with disease in family |
| G217-1 | M | KAT6B | NP_036462.2:p.Arg153Gln | de novo heterozygous | SBBYSS syndrome | VUS | probably causal | phenotype consistent with SBBYSS syndrome; bioinformatics predict that variant is damaging |
| G218-1 | M | ASH1L | NP_060959.2:p.Arg2691Ter | de novo heterozygous | autosomal dominant mental retardation 52 | unclassified | probably causal | phenotype consistent with reported cases; bioinformatics predict that variant is damaging |
| G231-1 | F | WDR26 | NP_001366332.1:p.Ala150Val | de novo heterozygous | Skraban-Deardorff syndrome | VUS | probably causal | phenotype consistent with Skraban-Deardorff syndrome; bioinformatics predict that variant is damaging |
| G235-1 | M | TRAF7 | NP_115647.2:p.Arg524Trp | de novo heterozygous | cardiac, facial, and digital anomalies with developmental delay | unclassified | probably causal | phenotype consistent with reported cases; bioinformatics predict that variant is damaging |
| G239-1 | M | HNRNPU | NP_114032.2:p.His451Pro | de novo heterozygous | early infantile epileptic encephalopathy 54 | unclassified | probably causal | phenotype consistent with reported cases; bioinformatics predict that variant is damaging |
| G241-1 | M | SZT2 | NP_001352928.1:p.Glu2560SerfsTer92 | compound heterozygous | early infantile epileptic encephalopathy 18 | likely pathogenic | probably causal | phenotype consistent with reported cases; likely pathogenic variant allelic to VUS; bioinformatics predict that both variants are damaging |
| NP_001352928.1:p.Thr3330Met | VUS | |||||||
| G248-1 | F | CRYBA2 | NP_476434.1:p.Gly65Arg | heterozygous (paternally inherited) | autosomal dominant cataract 42 | unclassified | probably causal | phenotype and family history characteristic of autosomal dominant congenital cataracts; variant segregates with cataracts in family; bioinformatics predict that variant is damaging |
| G256-1 | F | KAT6A | NP_006757.2:p.Pro933Ser | de novo heterozygous | autosomal dominant mental retardation 32 | VUS | probably causal | phenotype consistent with reported cases; bioinformatics predict that variant may be damaging |
| G259-1 | F | WDR45 | NM_001029896.2:c.436+5G>C | de novo heterozygous | neurodegeneration with brain iron accumulation 5 | VUS | definitely causal | phenotype characteristic of neurodegeneration with brain iron accumulation; bioinformatics predict that variant is damaging |
| G260-1 | M | MECP2 | NP_001104262.1:p.Gln256Leu | de novo hemizygous | X-linked intellectual disability disorder, Lubs type | VUS | probably causal | phenotype consistent with reported cases; bioinformatics predict that variant is damaging |
| G272-1 | M | SETD1B | NM_001353345.2:c.5589+1G>A | de novo heterozygous | intellectual developmental disorder with seizures and language delay | unclassified | probably causal | phenotype consistent with reported cases; bioinformatics predict that variant is damaging |
| G280-1 | F | CWF19L1 | NP_060764.3:p.Glu384Ter | compound heterozygous | autosomal recessive spinocerebellar ataxia 17 | likely pathogenic | probably causal | phenotype consistent with autosomal recessive spinocerebellar ataxia; likely pathogenic variant allelic to VUS; bioinformatics predict that both variants are damaging |
| NP_060764.3:p.Glu519del | VUS | |||||||
| G284-1 | F | ABL1 | NP_005148.2:p.Thr117Met | de novo heterozygous | congenital heart defects and skeletal malformation syndrome | VUS | probably causal | phenotype consistent with reported cases; bioinformatics predict that variant is damaging; functional studies support effect |
| G285-1 | F | GLRX5 | NP_057501.2:p.Met128Thr | homozygous | childhood-onset spasticity with hyperglycinemia | VUS | definitely causal | phenotype consistent with reported cases; bioinformatics predict that variant is damaging; biochemical studies consistent |
| G286-1 | M | IQCE | NP_689771.3:p.Asp112ValfsTer2 | compound heterozygous | post-axial polydactyly type A7 | unclassified | probably causal | phenotype characteristic of post-axial polydactyly; bioinformatics predict that both variants are damaging |
| NP_689771.3:p.Leu507AlafsTer10 | unclassified | |||||||
| G289-1 | F | CLCN4 | NP_001821.2:p.Gly182Ser | de novo heterozygous | Raynaud-Claes syndrome | VUS | probably causal | phenotype characteristic of Raynaud-Claes syndrome; bioinformatics predict that variant is damaging |
| G291-1 | F | KDM5A | NC_000012.11:g.460661_470642del | homozygous | autosomal recessive mental retardation 65 | VUS | probably causal | phenotype consistent with reported cases; bioinformatics predict that homozygous variant is damaging; homozygous variant also found in similarly affected sib |
| G291-4 | M | KDM5A | NC_000012.11:g.460661_470642del | homozygous | autosomal recessive mental retardation 65 | VUS | probably causal | phenotype consistent with reported cases; bioinformatics predict that homozygous variant is damaging; homozygous variant also found in similarly affected sib |
| G292-1 | M | SYT1 | NP_005630.1:p.Pro180Leu | de novo heterozygous | Baker-Gordon syndrome | unclassified | probably causal | phenotype consistent with Baker-Gordon syndrome; bioinformatics predict that variant is damaging |
| G297-1 | M | JARID2 | NP_004964.2:p.Arg1127Ter | de novo hemizygous | JARID2-neurodevelopmental syndrome | unclassified | probably causal | individual included in first published report of "new" genotype-phenotype association |
| G312-1 | F | NAA10 | NP_003482.1:p.Asn101Lys | de novo heterozygous | Ogden syndrome | VUS | probably causal | phenotype consistent with Ogden syndrome; bioinformatics predict that variant is damaging |
| G323-1 | M | GABBR2 | NP_005449.5:p.Pro282Leu | de novo heterozygous | neurodevelopmental disorder with poor language and loss of hand skills | VUS | probably causal | phenotype consistent with reported cases; bioinformatics predict that variant is damaging |
| G336-1 | M | KCNB1 | NP_004966.1:p.Glu71Ter | heterozygous (maternally inherited) | early infantile epileptic encephalopathy 26 | VUS | probably causal | phenotype and family history consistent with reported cases; bioinformatics predict that variant is damaging |
| G338-1 | F | KYNU | NP_003928.1:p.Lys121del | compound heterozygous | vertebral, cardiac, renal, and limb defects syndrome 2 | VUS | probably causal | phenotype characteristic of vertebral, cardiac, renal, and limb defects syndrome; variants are allelic and bioinformatics predict that both are damaging; functional studies demonstrated significant reduction in NAD levels |
| NP_003928.1:p.Ser345Arg | VUS | |||||||
| PLEKHA7 | NP_001316559.1:p.Asp191Asn | heterozygous (paternally inherited) | Mendelian non-syndromic cleft lip with or without cleft palate | unclassified | probably causal | phenotype consistent with reported cases; both sibs have orofacial clefting and variant; bioinformatics predict that variant is damaging | ||
| G338-4 | F | PLEKHA7 | NP_001316559.1:p.Asp191Asn | heterozygous (paternally inherited) | Mendelian non-syndromic cleft lip with or without cleft palate | unclassified | probably causal | phenotype consistent with reported cases; both sibs have orofacial clefting and variant; bioinformatics predict that variant is damaging |
| G345-1 | M | HISG1H1E | NP_005312.1:p.Gly124ArgfsTer71 | de novo heterozygous | Rahman syndrome | VUS | definitely causal | phenotype consistent with Rahman syndrome; bioinformatics predict that variant is damaging |
| G350-1 | F | TSC2 | NP_000539.2:p.His1543Arg | heterozygous (paternally inherited) | tuberous sclerosis 2 | VUS | definitely causal | phenotype characteristic of tuberous sclerosis; bioinformatics predict that variant is damaging |
| G356-1 | F | COL4A3BP | NP_001365958.1:p.Thr251Ala | de novo heterozygous | autosomal dominant mental retardation 34 | unclassified | probably causal | phenotype consistent with reported cases; bioinformatics predict that variant is damaging |
| G363-1 | M | FLNA | NM_001110556.2:c.4475-1G>T | hemizygous (maternally inherited) | periventricular nodular heterotopia I | VUS | probably causal | phenotype consistent with periventricular nodular heterotopia; bioinformatics predict that variant is damaging |
| G368-1 | M | KDM5C | NP_004178.2:p.Ser285Leu | hemizygous (maternally inherited) | X-linked syndromic mental retardation, Claes-Jensen type | VUS | probably causal | phenotype consistent with X-linked syndromic mental retardation, Claes-Jensen type; bioinformatics predict that variant may be damaging |
| G370-1 | M | RYR1 | NP_000531.2:p.Glu2987Gly | compound heterozygous | King-Denborough syndrome | VUS | probably causal | phenotype characteristic of King-Denborough syndrome; variants are allelic and bioinformatics predict that both are damaging |
| NP_000531.2:p.Asp4505His | VUS | |||||||
| G385-1 | M | CAMK2 | NP_057065.2:p.Ser341Thr | de novo heterozygous | autosomal dominant mental retardation 53 | VUS | probably causal | phenotype consistent with reported cases; bioinformatics predict that variant is damaging |
| G392-1 | M | KCNK9 | NP_001269463.1:p.Tyr205Cys | heterozygous (maternally inherited) | Birk-Barel mental retardation dysmorphism syndrome | VUS | probably causal | phenotype and family history consistent with Birk-Barel mental retardation dysmorphism syndrome; bioinformatics predict that variant is damaging |
| G393-1 | M | ERCC8 | NP_000073.1:p.Val362PhefsTer20 | homozygous | Cockayne syndrome, type A | VUS | definitely causal | phenotype characteristic of Cockayne syndrome; parental consanguinity; bioinformatics predict that variant is damaging |
| G396-1 | M | CHD3 | NP_001005273.1:p.Arg1172Gln | de novo heterozygous | Snijders Blok-Campeau syndrome | unclassified | definitely causal | phenotype characteristic of Snijders Blok-Campeau syndrome; bioinformatics predict that variant is damaging |
| G401-1 | F | CTCF | NP_006556.1:p.Asp357Asn | de novo heterozygous | autosomal dominant mental retardation 21 | VUS | probably causal | phenotype consistent with reported cases; bioinformatics predict variant is damaging |
| G402-4 | F | SMARCC2 | NP_001317217.1:p.Tyr679Ter | de novo heterozygous | Coffin-Siris syndrome 8 | VUS | probably causal | phenotype consistent with reported cases; bioinformatics predict variant is damaging |
| G404-1 | M | HNRNPU | NP_114032.2:p.Pro506Leu | de novo heterozygous | early infantile epileptic encephalopathy 54 | VUS | probably causal | phenotype consistent with reported cases; bioinformatics predict variant is damaging |
| G406-1 | F | H3F3A | NP_002098.1:p.Thr23Ile | de novo heterozygous | Bryant-Li-Bhoj neurodevelopmental syndrome 1 | VUS | probably causal | individual included in first published report of "new" genotype-phenotype association |
| G407-1 | M | JARID2 | NP_004964.2:p.Ile557ArgfsTer34 | de novo heterozygous | JARID2-neurodevelopmental disorder | unclassified | probably causal | individual included in first published report of "new" genotype-phenotype association |
| G421-1 | F | NEUROD2 | NP_006151.3:p.Glu130Lys | de novo heterozygous | early infantile epileptic encephalopathy 72 | unclassified | probably causal | phenotype consistent with reported cases; bioinformatics predict variant is damaging |
| G422-1 | M | DLL1 | NP_005609.3:p.Arg509Ter | heterozygous (paternally inherited) | neurodevelopmental disorder with non-specific brain abnormalities and with or without seizures | unclassified | definitely causal | individual included in first published report of "new" genotype-phenotype association |
| G447-1 | M | SLC6A8 | NP_005620.1:p.Phe248del | de novo hemizygous (mosaic) | cerebral creatine deficiency syndrome 1 | VUS | definitely causal | phenotype consistent with reported cases; bioinformatics predict variant is damaging |
| G462-1 | F | ASH1L | NP_060959.2:p.Glu1956Lys | de novo heterozygous | autosomal dominant mental retardation 52 | VUS | probably causal | phenotype consistent with reported cases; bioinformatics predict variant is damaging |
| G465-1 | F | ANKRD17 | NP_115593.3:p.Gln1787ArgfsTer5 | de novo heterozygous | Chopra-Amiel-Gordon syndrome | unclassified | definitely causal | individual included in first published report of "new" genotype-phenotype association |
| G468-1 | F | GNAO1 | NP_066268.1:p.Asp151Asn | heterozygous (inherited from mosaic mother) | early infantile epileptic encephalopathy 17 | VUS | probably causal | phenotype consistent with reported cases; bioinformatics predict variant is damaging |
| PTCH1 | NM_000264.5:c.654+3A>G | de novo heterozygous | basal cell nevus syndrome | VUS | probably causal | phenotype consistent with basal cell nevus syndrome; bioinformatics predict variant is damaging | ||
| G472-1 | F | GNB1 | NP_002065.1:p.Gly282Arg | de novo heterozygous | autosomal dominant mental retardation 42 | VUS | probably causal | phenotype consistent with reported cases; bioinformatics predict variant is damaging |
| G480-1 | M | MSX1 | NP_002439.2:p.Trp219Arg | heterozygous (paternally inherited) | orofacial cleft 5 | VUS | probably causal | phenotype and family history typical of hereditary orofacial clefting; bioinformatics predict variant is damaging; variant segregates with phenotype in family |
| G482-1 | F | SETD1B | NP_001340274.1:p.Gln1322Ter | de novo heterozygous | intellectual disability, epilepsy, and autism | unclassified | probably causal | phenotype consistent with reported cases; bioinformatics predict variant is damaging |
| G487-1 | F | DDX3X | NP_001347.3:p.Ile190Ser | de novo heterozygous | X-linked mental retardation 102 | VUS | definitely causal | phenotype consistent with reported cases; bioinformatics predict variant is damaging |
| G494-1 | M | EDEM3 | NP_079467.3:p.Arg314Ter | homozygous (maternally inherited isodisomy) | EDEM3-related disorder | unclassified | probably causal | individual included in first published report of "new" genotype-phenotype association |
| G498-1 | F | TANC2 | NP_079461.2:p.Arg1770Gly | de novo heterozygous | global developmental delay, cerebellar atrophy, and dysmorphic features (non-clinome) | unclassified | probably causal | phenotype consistent with reported cases; bioinformatics predict variant is damaging |
| G504-1 | F | TRRAP | NP_001362453.1:p.Thr10Met | de novo heterozygous | developmental delay with or without dysmorphic facies and autism | VUS | probably causal | individual included in first published report of "new" genotype-phenotype association |
| G508-1 | M | ERCC2 | NP_000391.1:p.Leu581Pro | Compound heterozygous | trichothiodystrophy | pathogenic | definitely causal | phenotype consistent with trichothiodystrophy; VUS allelic to pathogenic variant and predicted to be damaging |
| NP_000391.1:p.Arg658Cys | VUS | |||||||
| G536-1 | M | NF1 | NM_001042492.3:c.5609+1G>T | de novo heterozygous | neurofibromatosis 1 | unclassified | probably causal | phenotype consistent with neurofibromatosis 1; variant predicted as damaging; RNA studies demonstrated disruption of canonical splice site |
| G553-1 | F | TRIP12 | NP_001335252.1:p.Tyr1744Asp | heterozygous (inherited from mosaic father) | autosomal dominant mental retardation 49 | VUS | probably causal | phenotype consistent with reported cases; bioinformatics predict variant is damaging |
| G553-4 | M | TRIP12 | NP_001335252.1:p.Tyr1744Asp | heterozygous (inherited from mosaic father) | autosomal dominant mental retardation 49 | VUS | probably causal | phenotype consistent with reported cases; bioinformatics predict variant is damaging |
| G558-1 | F | CDH2 | NP_001783.2:p.Asp627Tyr | de novo heterozygous | syndromic neurodevelopmental disorder | unclassified | definitely causal | phenotype consistent with newly described disorder, bioinformatics predict variant is damaging |
| G559-1 | F | MPZL2 | NP_005788.1:p.Ile24MetfsTer22 | compound heterozygous | autosomal recessive deafness 111 | pathogenic | probably causal | phenotype consistent with reported cases; VUS allelic to pathogenic variant and predicted to be damaging |
| NP_005788.1:p.Asp93Val | VUS | |||||||
| G561-1 | F | ETV6 | NP_001978.1:p.Lys409Glu | heterozygous (maternally inherited) | thrombocytopenia 5 | VUS | probably causal | phenotype and family history consistent with thrombocytopenia 5; bioinformatics predict that variant is damaging; variant segregates with disease in family |
| G563-1 | F | MTHFS | NP_006432.1:p.Ala9GlyfsTer42 | homozygous | neurodevelopmental disorder with microcephaly, epilepsy, and hypomyelination | unclassified | probably causal | phenotype consistent with neurodevelopmental disorder with microcephaly, epilepsy, and hypomyelination; bioinformatics predict variant is damaging |
| G575-1 | M | COL5A1 | NP_000084.3:p.Pro1566Leu | heterozygous (maternally inherited) | Ehlers-Danlos syndrome type 1 | VUS | probably causal | phenotype consistent with Ehlers-Danlos syndrome; bioinformatics predict variant is damaging |