TABLE 3.

Clinical and/or molecular information for individuals seen in the clinic

Referred for diagnosis, genetic testing recommended and completed, clinical and molecular diagnosis (8)
Clinical diagnoses/phenotype	Gene or copy number variant	Coding sequence; protein variant	Zygosity	ACMG pathogenicity call	Inheritance if known	Type of genetic test performed to obtain result	Laboratory testing performed	Additional comments
Hypohidrotic ectodermal dysplasia	NM_001399.4 EDA NM_025216.2 WNT10A	c.929A>G; p.Y310C c.682T>A; p.F228I	Hemizygous Heterozygous	Likely pathogenic Pathogenic	Maternally inherited Maternally inherited (mother affected)	Gene panel, SNP microarray	Gene DX, CHOP DGD	EDA variant classified by GeneDX as pathogenic; our classification is likely pathogenic
Ichthyosis vulgaris, developmental delay, submucous cleft palate, cryptorchidism	NM_002016.1 FLG	c.1501C>T; p.r501* c.2282_2285del4; p.S761Cfs*36	Heterozygous Heterozygous	Pathogenic Pathogenic	Paternally inherited Maternally inherited	Karyotype, exome sequencing	CHOP DGD	FLG only explains skin manifestations
Nevus comedonicus syndrome	NM_033116.5 NEK9	c.1755_1757del; p.T586del	(mean allele frequency 28%, nevus)	Likely pathogenic	NA	Single gene testing	Prevention genetics
PIK3CA-related Overgrowth Spectrum	NM_006218.2 PIK3CA	c.1624G>A; p.E542K	“Allele frequency consistent with somatic origin” from epidermal nevus, absent from blood	Pathogenic	NA	Gene panel and single gene (sent simultaneously)	GPS at WUSTL
Blue rubber bleb nevus syndrome	NM_000459.3 TEK	c.2744G>A; p.R915H	Heterozygous	Pathogenic	Parents not interested	Gene panel	CTGT
Capillary malformation arteriovenous malformation syndrome	NM_002890.2 RASA1	c.1659C>A; p. Y553*	Heterozygous		Unknown (assumed paternal based on family history)	Gene panel	UAB
Xeroderma pigmentosum type C	NM_004628.4 XPC	c.420_423del; p.E141Lfs*6 c.1677C>A; p.Y559*	Heterozygous Heterozygous	Pathogenic Likely pathogenic	Maternal Paternal	Gene panel	Prevention genetics
TANC2 related neurodevelopmental disorder and mastocytosis	NM_025185.3 TANC2	c.4955_4967delGAGTCAG CCAGAG; p.G1652Afs*13	Heterozygous	Likely pathogenic	Suspected maternal mosaic	Exome sequencing	CHOP DGD	TANC2 only explains neurodevelopmental issues and not the mastocystosis
Referred for diagnosis, genetic testing recommended and completed, clinical diagnosis only (8)
Clinical diagnoses/phenotype	Gene or copy number variant	Coding sequence, variant	Zygosity	ACMG pathogenicity call	Inheritance if known	Type of genetic test performed to obtain result	Laboratory testing performed	Additional comments
Piebaldism	NM_000222.2 KIT	c.2468A>G; p.Y823C	Heterozygous	VUS	Unknown	Gene panel	Gene DX
Palmoplantar keratoderma	NM_006121.3 KRT1	c_723_740del; p.R241_K246del	Heterozygous	VUS	Maternally inherited (mother affected)	Gene panel; exome sequencing	Gene DX
Thyroxine-binding globulin deficiency with alopecia universalis	NM_000354.5 SERPINA7	c.1234C>G; p.P412A	Heterozygous	VUS	Paternally inherited	Single gene, SNP microarray, exome sequencing	CHOP DGD	Patient was known to have low thyroxine-binding globulin levels at the time of evaluation.
Hypohidrotic ectodermal dysplasia	NM_145861.2 EDARADD	c.392C>T; p.P131L	Homozygous	VUS	Pending	Gene panel, SNP microarray	Invitae, CHOP DGD
In utero drug exposure	NA							Noonan syndrome gene panel negative
Blue rubber bleb nevus syndrome	NA							TEK, GLMN sequencing and deletion duplication testing from blood and lesion negative
Ectodermal dysplasia (2)	NA					Ectodermal dysplasia gene panel	Invitae	Negative
Referred for diagnosis, genetic testing recommended and completed, no diagnosis (6)
Clinical diagnoses/phenotype	Gene or copy number variant	Coding sequence, variant	Zygosity	ACMG pathogenicity call	Inheritance if known	Type of genetic test performed to obtain result	Laboratory testing performed	Additional comments
Ichthyosis vulgaris	NM_002016.1 FLG	c.9793G>A; p.G3265R	Heterozygous	Likely benign	Maternally inherited	Chromosome breakage studies, SNP microarray, exome sequencing	Cincinatti Children’s, CHOP DGD	FLG variant classified as VUS by CHOP DGD, our classification is likely benign
Developmental delay and mastocytosis	NA							Negative SNP microarray, fragile X, quintet exome with sister as proband
Developmental delay and mastocytosis	NA							Negative quintet exome with sister as proband
Expressive language delay, motor delay, multiple hemangiomas, connective tissue nevi, cor triatriatum, and aberrant right subclavian artery	NM_006364.3 SEC23A NM_001266856 GNA11	c.560A>G; p.Y187C c.230A>G; p.K77R	Heterozygous Heterozygous	VUS VUS	Maternally inherited Paternally inherited	SNP microarray, trio exome sequencing, somatic overgrowth panel	CHOP DGD, Penn GDL	SEC23A deletion/duplication testing to GeneDX negative
Developmental delay and xerosis	NA					SNP microarray, fragile X	CHOP DGD	Negative
Atopic dermatis and congenital anomaly of the kidney and urinary tract	NM_000296 PKD1	c.776G>A; p.C259Y	Heterozygous	Likely pathogenic	Unknown	Kidney-seq	IIHG	14 additional VUSes; Awaiting authorization for exome sequencing
Referred for diagnosis, genetic testing recommended but not completed (4)
Clinical diagnoses/phenotype	Gene or copy number variant	Coding sequence, variant	Zygosity	ACMG pathogenicity call	Inheritance if known	Type of genetic test performed to obtain result	Laboratory testing performed	Additional comments
X-linked ichthyosis	NA							Parents declined
Multiple capillary Malformations	NA							Teseting not approved by insurance
Common variable immunodeficiency, telangiectasias, renal hypoplasia	NA							Out of pocket cost too high to proceed with testing
Familial hyperpigmentation with or without hypopigmentation	NA							Parents interested in testing, not approved by insurance
Referred for diagnosis, no genetic testing recommended (10)
Clinical diagnoses/phenotype	Gene or copy number variant	Coding sequence, variant	Zygosity	ACMG pathogenicity call	Inheritance if known	Type of genetic test performed to obtain result	Laboratory testing performed	Additional comments
Isolated port wine stain	NA
Pseudoxanthoma elasticum	NA							Opted for testing at specialty clinic
Atopic dermatitis (3)	NA
Ichthyosis vulgaris	NA
Benign pigmentary mosaicism (2)	NA
Familial hyperpigmentation with or without hypopigmentation	NA
Premature graying of hair, progressive areas of hyperpigmentation, developmental delay	NA							Testing sent at outside institution
Referred for counseling and diagnosis (4)
Clinical diagnoses/phenotype	Gene or copy number variant	Coding sequence, variant	Zygosity	ACMG pathogenicity call	Inheritance if known	Type of genetic test performed to obtain result	Laboratory testing performed	Additional comments
Oculocutaneous albinism	NM_000275.2 OCA2	c.819_822delinsGGTC; p.N273_W274delinsKV c.1699G>A; p.E567K	Unknown	Pathogenic VUS	Unknown	Gene panel, enzyme testing	Denver genetics	No pathogenicity calls or NM transcript number; performed in 2011
Idiopathic infantile hypercalcemia and epidermal inclusion cysts (2, siblings)	NM_000782.4 CYP24A1	c.428_430delAAG; p.E143del c.1186C>T; p.R396W	Compound heterozygous	Pathogenic (previously reported)	Maternal, paternal	Research quad exome	Dupont
Sturge–Weber syndrome	NA	NA	NA	NA	NA	NA	NA
Referred for counseling (5)
Clinical diagnoses/phenotype	Gene or copy number variant	Coding sequence, variant	Zygosity	ACMG pathogenicity call	Inheritance if known	Type of genetic test performed to obtain result	Laboratory testing performed	Additional comments
Hermansky–Pudlak syndrome type 3	NM_032383.4 HPS3	c.−2874_217 + 673del	Homozygous	Pathogenic	Maternal, paternal	Gene panel; SNP microarray	Molecular vision laboratoryArray: CHOP DGD
Patau syndrome with severe acne	mos 47,XY,+13[18]/46,XY[2]	NA	NA	NA	NA	Karyotype	Jefferson
Gorlin syndrome	arr[hg19] 9q22.2q22.33 (93,745,280–100,395,565)x1	NA	NA	NA	NA	Microarray	Quest
Tuberous sclerosis 2	NM_000548.3 TSC2	c.2194C>T; p.Q732*	Heterozygous	Pathogenic	Unknown	Gene panel	Athena (performed in 2006)
Keratitis–ichthyosis–deafness syndrome	NM_004004.5 GJB2	c.148G>A; p.D50N	Heterozygous	Pathogenic	de novo	Single gene	CHOP DGD

Abbreviations: CHOP DGD, The Children’s Hospital of Philadelphia Division of Genomic Diagnostics; GPS at WUSTL, Genomic and Pathology Services at Washington University in St. Louis; CTGT, connective tissue gene tests; UAB, University of Alabama; Penn GDL, University of Pennsylvania Genetic Diagnostic Laboratory; IIHG, Iowa Institute of Human Genetics.