Submissions for variant NM_000264.5(PTCH1):c.4080C>T (p.Ser1360=)

dbSNP: rs62637631

Total submissions: 15

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000078464	SCV000110320	benign	not specified	2013-07-30	criteria provided, single submitter	clinical testing
Invitae	RCV000204296	SCV000261833	benign	Gorlin syndrome	2024-02-01	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000078464	SCV000303359	benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000276641	SCV000481248	benign	Holoprosencephaly 7	2018-01-12	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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Illumina Laboratory Services, Illumina	RCV000204296	SCV000481249	benign	Gorlin syndrome	2018-01-12	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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Ambry Genetics	RCV000492528	SCV000581064	likely benign	Hereditary cancer-predisposing syndrome	2016-07-11	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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000589777	SCV000696375	benign	not provided	2016-08-30	criteria provided, single submitter	clinical testing	Variant summary: The PTCH1 c.4080C>T (p.Ser1360Ser) variant causes a synonymous change involving a non-conserved nucleotide with 5/5 splice prediction tools predicting no significant affect on splicing. The variant of interest was observed in the large, broad control population, ExAC, with an allele frequency of 468/116042 (1/247, 2 homozygotes), which significantly exceeds the expected allele frequency for a pathogenic PTCH1 variant of 1/58479, suggesting this variant is likely a benign polymorphism. In addition, multiple clinical diagnostic laboratories have cited the variant as "benign." Therefore, the variant of interest has been classified as Benign.
GeneDx	RCV000589777	SCV001945667	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000078464	SCV002046713	benign	not specified	2021-03-19	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000492528	SCV002535148	benign	Hereditary cancer-predisposing syndrome	2020-11-06	criteria provided, single submitter	curation
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV000204296	SCV004017130	benign	Gorlin syndrome	2023-07-07	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000589777	SCV004160179	benign	not provided	2024-03-01	criteria provided, single submitter	clinical testing	PTCH1: BP4, BP7, BS1, BS2
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000589777	SCV004562972	benign	not provided	2023-09-12	criteria provided, single submitter	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000589777	SCV001797392	likely benign	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000078464	SCV001807896	benign	not specified		no assertion criteria provided	clinical testing