Submissions for variant NM_000264.5(PTCH1):c.2319C>T (p.Asp773=)

gnomAD frequency: 0.00017  dbSNP: rs141134542

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000198611	SCV000253179	benign	Gorlin syndrome	2024-01-29	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000492074	SCV000581002	likely benign	Hereditary cancer-predisposing syndrome	2017-02-08	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.
Illumina Laboratory Services, Illumina	RCV000198611	SCV001332006	likely benign	Gorlin syndrome	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Illumina Laboratory Services, Illumina	RCV001169318	SCV001332007	likely benign	Holoprosencephaly 7	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
GeneDx	RCV001675666	SCV001894806	likely benign	not provided	2021-06-17	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV001675666	SCV004160199	likely benign	not provided	2022-11-01	criteria provided, single submitter	clinical testing	PTCH1: BP4, BP7
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV001675666	SCV004219181	benign	not provided	2022-03-11	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004553077	SCV004787312	likely benign	PTCH1-related disorder	2022-02-12	criteria provided, single submitter	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).