Submissions for variant NM_000264.5(PTCH1):c.2173C>T (p.Pro725Ser)

gnomAD frequency: 0.00098  dbSNP: rs149258400

Total submissions: 17

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001083270	SCV000166301	benign	Gorlin syndrome	2024-02-01	criteria provided, single submitter	clinical testing
GeneDx	RCV000121884	SCV000514297	benign	not specified	2015-09-18	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Ambry Genetics	RCV000492416	SCV000581043	likely benign	Hereditary cancer-predisposing syndrome	2018-05-03	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	RCV001166906	SCV001329331	benign	Holoprosencephaly 7	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign.
Illumina Laboratory Services, Illumina	RCV001083270	SCV001329332	benign	Gorlin syndrome	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign.
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden	RCV000034563	SCV002011174	likely benign	not provided	2021-11-03	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000492416	SCV002526843	likely benign	Hereditary cancer-predisposing syndrome	2022-02-11	criteria provided, single submitter	curation
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000121884	SCV002765999	likely benign	not specified	2022-11-03	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000121884	SCV002773933	benign	not specified	2021-07-21	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000034563	SCV004160203	likely benign	not provided	2024-08-01	criteria provided, single submitter	clinical testing	PTCH1: BS1
Breakthrough Genomics, Breakthrough Genomics	RCV000034563	SCV005222453	likely benign	not provided		criteria provided, single submitter	not provided
Biesecker Lab/Clinical Genomics Section, National Institutes of Health	RCV000034563	SCV000043457	variant of unknown significance	not provided	2012-07-13	no assertion criteria provided	research	Converted during submission to Uncertain significance.
ITMI	RCV000121884	SCV000086086	not provided	not specified	2013-09-19	no assertion provided	reference population
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000034563	SCV001799470	likely benign	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000034563	SCV001807086	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000034563	SCV001975539	likely benign	not provided		no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004549397	SCV004753745	likely benign	PTCH1-related disorder	2020-09-24	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).