Submissions for variant NM_000264.5(PTCH1):c.3919C>T (p.Pro1307Ser)

gnomAD frequency: 0.00021  dbSNP: rs574880967

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000119211	SCV000153953	likely benign	Gorlin syndrome	2024-01-31	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000567632	SCV000674515	likely benign	Hereditary cancer-predisposing syndrome	2020-11-13	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.
Fulgent Genetics, Fulgent Genetics	RCV000764839	SCV000895995	uncertain significance	Basal cell carcinoma, susceptibility to, 1; Gorlin syndrome; Holoprosencephaly 7	2018-10-31	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000119211	SCV001329124	benign	Gorlin syndrome	2018-03-06	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	RCV001166720	SCV001329125	likely benign	Holoprosencephaly 7	2018-03-06	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.
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden	RCV003237716	SCV002009308	uncertain significance	not provided	2021-11-03	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000567632	SCV002526921	likely benign	Hereditary cancer-predisposing syndrome	2021-11-16	criteria provided, single submitter	curation
PreventionGenetics, part of Exact Sciences	RCV003415902	SCV004108791	uncertain significance	PTCH1-related condition	2023-08-18	criteria provided, single submitter	clinical testing	The PTCH1 c.3919C>T variant is predicted to result in the amino acid substitution p.Pro1307Ser. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.043% of alleles in individuals of European (Non-Finnish) descent in gnomAD (https://gnomad.broadinstitute.org/variant/chr9-98209619-G-A) and has been reported in ClinVar as benign/likely benign/uncertain (https://preview.ncbi.nlm.nih.gov/clinvar/variation/132753/). This variant could be benign. However, at this time, its clinical significance is uncertain due to the absence of conclusive functional and genetic evidence.
CeGaT Center for Human Genetics Tuebingen	RCV003237716	SCV004160182	likely benign	not provided	2023-06-01	criteria provided, single submitter	clinical testing	PTCH1: BP4