Submissions for variant NM_000264.5(PTCH1):c.2678G>A (p.Arg893His)

gnomAD frequency: 0.00014  dbSNP: rs138154222

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000364653	SCV000481290	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.
Illumina Laboratory Services, Illumina	RCV000272169	SCV000481291	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.
Invitae	RCV000364653	SCV000560040	benign	Gorlin syndrome	2024-01-31	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000492538	SCV000581018	likely benign	Hereditary cancer-predisposing syndrome	2018-06-20	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.
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	RCV000034567	SCV000610408	likely benign	not provided	2017-06-05	criteria provided, single submitter	clinical testing
GeneDx	RCV000034567	SCV000984148	likely benign	not provided	2019-11-26	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 29642553, 24942795, 16109989, 22703879)
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000034567	SCV004219189	benign	not provided	2022-04-28	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000034567	SCV004698877	benign	not provided	2024-02-01	criteria provided, single submitter	clinical testing	PTCH1: BS1, BS2
Biesecker Lab/Clinical Genomics Section, National Institutes of Health	RCV000034567	SCV000043453	variant of unknown significance	not provided	2012-07-13	no assertion criteria provided	research	Converted during submission to Uncertain significance.