Submissions for variant NM_000264.5(PTCH1):c.113G>A (p.Gly38Glu)

dbSNP: rs143494325

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000200738	SCV000254451	likely benign	Gorlin syndrome	2024-01-22	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000492756	SCV000581016	benign	Hereditary cancer-predisposing syndrome	2019-10-16	criteria provided, single submitter	clinical testing	This alteration is classified as benign based on a combination of the following: 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.
St. Jude Molecular Pathology, St. Jude Children's Research Hospital	RCV000761034	SCV000890949	uncertain significance	Craniopharyngioma	2016-10-31	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV001818487	SCV002066069	uncertain significance	not specified	2021-06-17	criteria provided, single submitter	clinical testing	DNA sequence analysis of the PTCH1 gene demonstrated a sequence change, c.113G>A, in exon 1 that results in an amino acid change, p.Gly38Glu. This sequence change has been described in gnomAD with a frequency of 0.016% in the Non-Finnish European sub-population (dbSNP rs143494325). The p.Gly38Glu change affects a moderately conserved amino acid residue located in a domain of the PTCH1 protein that is known to be functional. The p.Gly38Glu substitution appears to be tolerated using several in-silico pathogenicity prediction tools (SIFT, PolyPhen2, Align GVGD, REVEL).One recent study reported an individual with congenital embryonal rhabdomyosarcoma who was compound heterozygous for this variant in PTCH1 and another missense change in the PTCH2 (PMID: 29230040). Due to the lack of sufficient evidences, the clinical significance of the p.Gly38Glu change remains unknown at this time.
Sema4, Sema4	RCV000492756	SCV002526792	likely benign	Hereditary cancer-predisposing syndrome	2021-08-20	criteria provided, single submitter	curation
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV001723770	SCV002774225	likely benign	not provided	2023-01-25	criteria provided, single submitter	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV001723770	SCV001959458	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001723770	SCV001974212	likely benign	not provided		no assertion criteria provided	clinical testing