Submissions for variant NM_000264.5(PTCH1):c.4049G>A (p.Arg1350Gln)

gnomAD frequency: 0.00001  dbSNP: rs978722722

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000699814	SCV000828542	uncertain significance	Gorlin syndrome	2024-01-10	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 1350 of the PTCH1 protein (p.Arg1350Gln). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with PTCH1-related conditions. ClinVar contains an entry for this variant (Variation ID: 577136). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt PTCH1 protein function with a negative predictive value of 95%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Fulgent Genetics, Fulgent Genetics	RCV000764836	SCV000895992	uncertain significance	Basal cell carcinoma, susceptibility to, 1; Gorlin syndrome; Holoprosencephaly 7	2018-10-31	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV001021745	SCV001183397	likely benign	Hereditary cancer-predisposing syndrome	2023-01-19	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.
Baylor Genetics	RCV004569359	SCV005052543	uncertain significance	Basal cell carcinoma, susceptibility to, 1	2023-11-14	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004547867	SCV004779060	likely benign	PTCH1-related disorder	2023-02-21	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).