TABLE 3.
LMNA variants and related features found in our pediatric cohort.
| Patient | Gene | Nucleotide change | Protein change | dbSNP | gnomAD (MAF%) | HGMD disease | ClinVar disease | ACMG score | Father | Mother | Other relatives |
|---|---|---|---|---|---|---|---|---|---|---|---|
| 1 | GAA | c.1781G>A | p.Arg594His | rs775450536 | 2/248732 (0.0008%) | CM121193, GSD | P, GSD | LP | - | + | Sister - |
| LMNA | c.745C>T | p.Arg249Trp | rs121912496 | NA | CM083718, MD | P/LP, MD | LP | - | - | Sister- | |
| 2 | AGRN | c.2218C>T | p.Arg740Ter | NA | NA | NA | NA | LP | - | + | Sister + |
| FLNC | c.1932delT | p.Cys644TrpfsTer27 | NA | NA | NA | NA | LP | - | + | Sister- | |
| LMNA | c.745C>T | p.Arg249Trp | rs121912496 | NA | CM083718, MD | P/LP, MD | LP | - | - | Sister- | |
| 3† | LMNA | c.116A>G | p.Asn39Ser | rs57983345 | NA | CM083713, MD | P, CMT | P | - | - | NA |
| 4 | LMNA | c.91_93delGAG | p.Glu31del | rs864309525 | NA | CD156162, MD | LP, MD | LP | - | - | NA |
| 5 | GAA | c.1952G > A | p.Gly651Asp | rs939350425 | NA | NA | VUS | LP | - | + | Siblings - |
| LMNA | c.1358G > C | p.Arg453Pro | rs267607598 | NA | CM083716, MD | NA | LP | - | - | Siblings - | |
| 6 | LMNA | c.745C > T | p.Arg249Trp | rs121912496 | NA | CM083718, MD | P/LP, MD | LP | - | - | NA |
| 7 | LAMP2 | c.413A > G | p.Asp138Gly | NA | NA | NA | NA | VUS-LP | - | + | Brother - |
| LMNA | c.116A > G | p.Asn39Ser | rs57983345 | NA | CM083713, MD | P, CMT | P | - | - | Brother - | |
| 8 | LMNA | c.746G > A | p.Arg249Gln | rs59332535 | NA | CM1617006, MD, ED | P, MD | P | - | - | NA |
| 9 | LMNA | c.91delG | p.Glu31ArgfsTer65 | NA | NA | NA | NA | P | - | - | NA |
| 10 | LMNA | c.89A > C | p.Gln30Pro | NA | NA | NA | NA | LP | - | - | Brother - |
| 11 | LMNA | c.1487_1488 + 9del | NA | NA | CD1711480, MD | NA | P | - | + | Brother - | |
| NEB | c.17376_17381del | p.Met5792_Asp5794delinsIle | rs765184893 | 9/247156 (0.0036%) | NA | NA | VUS-LP | - | + | Brother + | |
| 12 | LMNA | c.1616C > T | p.Ala539Val | NA | NA | NA | NA | LP | - | - | NA |
| 13 | LMNA | c.112C > T | p.Leu38Phe | NA | NA | NA | NA | LP | - | - | NA |
| 14 | LMNA | c.745C > T | p.Arg249Trp | rs121912496 | NA | CM083718, MD | P/LP, MD | LP | - | - | NA |
| 15 | LMNA | c.812T > G | p.Leu271Arg | NA | NA | NA | NA | LP | - | - | NA |
| 16 | LMNA | c.1364G > C | p.Arg455Pro | rs267607597 | NA | CM111722, MD | NA | LP | - | - | NA |
| 17 | LMNA | c.810 + 1G > C | rs267607632 | NA | NA | P, MD | P | - | - | NA | |
| 18 | COL6A3 | c.8883delA | p.Lys2961AsnfsTer40 | NA | NA | NA | NA | LP | + | - | NA |
| GAA | c.1933G>A | p.Asp645Asn | rs368438393 | 2/242414 (0.0008%) | CM980804, GSD | LP, GSD | LP | - | + | NA | |
| LMNA | c.108G>T | p.Gln36His | NA | NA | NA | NA | LP | + | - | NA | |
| 19 | LMNA | c.104T>A | p.Leu35Gln | NA | NA | NA | NA | LP | - | - | NA |
| 20 | LMNA | c.1357C>T | p.Arg453Trp | rs58932704 | NA | CM990813, MD | P/LP, MD | LP | - | - | NA |
| 21 | LMNA | c.1357C>T | p.Arg453Trp | rs58932704 | NA | CM990813, MD | P/LP, MD | LP | - | - | NA |
| 22† | DYSF | c.5546G>A | p.Arg1849Lys | rs786205084 | NA | NA | LP, MD | LP | - | + | Brother + |
| LMNA | c.91G>A | p.Glu31Lys | rs1228406418 | NA | CM123360, MD | P, CMT | LP | - | - | Brother - | |
| 23,24 twins | CHRND | c.919_920delCCinsAG | p.Pro307Ser | NA | NA | NA | NA | VUS-LP | - | + | Brother +/Twin + |
| LMNA | c.117T>G | p.Asn39Lys | NA | NA | CM156123, MD | NA | LP | - | - | Brother -/Twin + | |
| 25 | LMNA | c.94_96delAAG | p.Lys32del | rs60872029 | NA | CD033712, MD, ED | P, MD | P | - | - | NA |
| 26 | LMNA | c.745C>T | p.Arg249Trp | rs121912496 | NA | CM083718, MD | P/LP, MD | LP | - | - | NA |
dbSNP, single nucleotide polymorphism database. ACMG, score, the American College of Medical Genetics and Genomics score. ClinVar, Clinically relevant Variation database. CMT, Charcot-Marie-Tooth. ED, Emery-Dreifuss. GnomAD (MAF%), Genome Aggregation Database (minor allele frequency %). GSD, Glycogen Storage Disease. HGMD, the Human Gene Mutation Database. LP, Likely Pathogenic. MD, muscular dystrophy. NA, not available. P, Pathogenic. †, sudden death. VUS-LP, variant of unknown significance with highly suspicious likely pathogenic role.