Submissions for variant NM_000264.5(PTCH1):c.2222C>T (p.Ala741Val)

gnomAD frequency: 0.00020  dbSNP: rs2227971

Total submissions: 13

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000123008	SCV000166303	benign	Gorlin syndrome	2024-01-30	criteria provided, single submitter	clinical testing
GeneDx	RCV000121885	SCV000171225	benign	not specified	2014-01-13	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.
Oral and Maxillofacial Surgery, Tokyo Medical and Dental University	RCV000123008	SCV000255958	benign	Gorlin syndrome	2015-09-28	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000560992	SCV000674468	likely benign	Hereditary cancer-predisposing syndrome	2019-03-21	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.
Illumina Laboratory Services, Illumina	RCV001166382	SCV001328755	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 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	RCV000123008	SCV001328756	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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Genetic Services Laboratory, University of Chicago	RCV000121885	SCV002066065	likely benign	not specified	2021-06-28	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000560992	SCV002526848	likely benign	Hereditary cancer-predisposing syndrome	2020-12-31	criteria provided, single submitter	curation
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV001528432	SCV002773937	benign	not provided	2022-10-07	criteria provided, single submitter	clinical testing
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV000123008	SCV004017168	benign	Gorlin syndrome	2023-07-07	criteria provided, single submitter	clinical testing
ITMI	RCV000121885	SCV000086088	not provided	not specified	2013-09-19	no assertion provided	reference population
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV001528432	SCV001740178	likely benign	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV001528432	SCV001807688	likely benign	not provided		no assertion criteria provided	clinical testing