Submissions for variant NM_000264.5(PTCH1):c.3954G>A (p.Pro1318=)

gnomAD frequency: 0.00054  dbSNP: rs45529536

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000197787	SCV000253193	benign	Gorlin syndrome	2024-02-01	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000492597	SCV000581044	likely benign	Hereditary cancer-predisposing syndrome	2015-02-17	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	RCV000197787	SCV001328571	likely 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Illumina Laboratory Services, Illumina	RCV001166718	SCV001329121	likely 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
GeneDx	RCV001528334	SCV001835348	likely benign	not provided	2018-10-31	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000492597	SCV002526923	likely benign	Hereditary cancer-predisposing syndrome	2021-07-01	criteria provided, single submitter	curation
CeGaT Center for Human Genetics Tuebingen	RCV001528334	SCV004160181	likely benign	not provided	2022-12-01	criteria provided, single submitter	clinical testing	PTCH1: BP4, BP7
PreventionGenetics, part of Exact Sciences	RCV003967529	SCV004780720	likely benign	PTCH1-related condition	2023-01-23	criteria provided, single submitter	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).
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV001528334	SCV001739910	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001528334	SCV001964563	likely benign	not provided		no assertion criteria provided	clinical testing