Submissions for variant NM_000264.5(PTCH1):c.4001G>A (p.Ser1334Asn)

gnomAD frequency: 0.00016  dbSNP: rs200620662

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000167997	SCV000218648	likely benign	Gorlin syndrome	2025-02-04	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV001021641	SCV001183283	likely benign	Hereditary cancer-predisposing syndrome	2019-03-25	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
GeneDx	RCV001589046	SCV001816312	likely benign	not provided	2020-06-05	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Fulgent Genetics, Fulgent Genetics	RCV002492679	SCV002799904	likely benign	Basal cell carcinoma, susceptibility to, 1; Gorlin syndrome; Holoprosencephaly 7	2021-09-02	criteria provided, single submitter	clinical testing
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV005230028	SCV005873448	uncertain significance	not specified	2025-03-04	criteria provided, single submitter	clinical testing	Classification criteria: BP4
PreventionGenetics, part of Exact Sciences	RCV004552935	SCV004120263	uncertain significance	PTCH1-related disorder	2024-07-24	no assertion criteria provided	clinical testing	The PTCH1 c.4001G>A variant is predicted to result in the amino acid substitution p.Ser1334Asn. To our knowledge, this variant has not been reported in association with disorders in the literature. This variant is reported in 0.021% of alleles in individuals of European (Non-Finnish) descent in gnomAD and has conflicting interpretations of pathogenicity in ClinVar ranging from likely benign to uncertain (https://www.ncbi.nlm.nih.gov/clinvar/variation/188130/). Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.