Submissions for variant NM_000264.5(PTCH1):c.3141T>G (p.Leu1047=)

gnomAD frequency: 0.03773  dbSNP: rs2066835

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
PreventionGenetics, part of Exact Sciences	RCV000245421	SCV000303344	benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000352228	SCV000481278	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	RCV000391414	SCV000481279	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.
Invitae	RCV000391414	SCV000560033	benign	Gorlin syndrome	2024-02-01	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000492323	SCV000581060	benign	Hereditary cancer-predisposing syndrome	2016-04-01	criteria provided, single submitter	clinical testing	This alteration is classified as 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	RCV000588210	SCV000696377	benign	not provided	2016-05-24	criteria provided, single submitter	clinical testing	Variant summary: The c.3141T>C (p.Leu1047=) in PTCH1 gene is a synonymous change that involves a non-conserved nucleotide. 5/5 programs in Alamut predict that this variant does not affect normal splicing, however no functional studies supporting this notion were published at the time of evaluation. The variant is present in the control population dataset of ExAC at frequency of 0.0239 (2894/120918 chrs tested), predominantly in individuals of African origin (0.1145; 1179/10292 control chrs) including numerous homozygous occurrences. This frequency exceeds the maximal expected frequency of a pathogenic allele (0.00007) in this gene. The variant of interest was cited as Polymorphism in published reports (Sun, 2008 and Musani, 2013). Taking together, the variant was classified as Benign.
GeneDx	RCV000588210	SCV001916286	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000245421	SCV002047197	benign	not specified	2021-05-28	criteria provided, single submitter	clinical testing
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV000391414	SCV004017132	benign	Gorlin syndrome	2023-07-07	criteria provided, single submitter	clinical testing