Submissions for variant NM_000264.5(PTCH1):c.1234G>T (p.Ala412Ser)

gnomAD frequency: 0.00010  dbSNP: rs370354759

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
CSER _CC_NCGL, University of Washington	RCV000148764	SCV000190501	uncertain significance	Gorlin syndrome	2014-06-01	criteria provided, single submitter	research	Low GERP score may suggest that this variant may belong in a lower pathogenicity class
GeneDx	RCV001719925	SCV000521004	likely benign	not provided	2020-02-11	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 16508594, 25637381)
Invitae	RCV000148764	SCV000549093	likely benign	Gorlin syndrome	2024-01-28	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV001010476	SCV001170680	likely benign	Hereditary cancer-predisposing syndrome	2020-03-16	criteria provided, single submitter	clinical testing	This alteration is classified as likely 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.
PreventionGenetics, part of Exact Sciences	RCV003415984	SCV004116288	uncertain significance	PTCH1-related condition	2022-10-26	criteria provided, single submitter	clinical testing	The PTCH1 c.1234G>T variant is predicted to result in the amino acid substitution p.Ala412Ser. This variant was reported in an individual with nevoid basal cell carcinoma syndrome (Pruvost-Balland et al. 2006. PubMed ID: 16508594). This variant is reported in 0.0080% of alleles in individuals of African descent in gnomAD (http://gnomad.broadinstitute.org/variant/9-98240450-C-A) and has conflicting interpretations in ClinVar of likely benign and uncertain (https://www.ncbi.nlm.nih.gov/clinvar/variation/161357/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV001719925	SCV001963410	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001719925	SCV001965049	likely benign	not provided		no assertion criteria provided	clinical testing