Submissions for variant NM_000264.5(PTCH1):c.1665T>C (p.Asn555=)

gnomAD frequency: 0.12597  dbSNP: rs1805155

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
PreventionGenetics, part of Exact Sciences	RCV000245867	SCV000303327	benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000284231	SCV000481320	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	RCV000346189	SCV000481321	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.
Ambry Genetics	RCV000492326	SCV000580997	benign	Hereditary cancer-predisposing syndrome	2014-12-04	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.
Invitae	RCV000284231	SCV000622926	benign	Gorlin syndrome	2024-02-01	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000587264	SCV000696371	benign	not provided	2016-05-24	criteria provided, single submitter	clinical testing	Variant summary: The PTCH1 c.1665T>C (p.Asn555Asn) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. One in silico tool predicts a polymorphism outcome for this variant. 5/5 splice prediction tools predict no significant impact on normal splicing. ESE finder predicts that this variant may affect ESE site of SRp55. This variant was found in 12470/115592 control chromosomes (719 homozygotes) at a frequency of 0.1078794, which is approximately 6295 times the estimated maximal allele frequency of a pathogenic PTCH1 variant (0.0000171), suggesting this variant is a benign polymorphism. This variant has been reported in multiple affected individuals in co-occurrence with different pathogenic variants (Pastorino_Human_Mutation_2005), further supporting the benign classification. In addition, another clinical diagnostic laboratory classified this variant as benign. Taken together, this variant is classified as benign.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000587264	SCV001156988	benign	not provided	2023-11-29	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000492326	SCV002526815	benign	Hereditary cancer-predisposing syndrome	2020-01-30	criteria provided, single submitter	curation
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV000284231	SCV004017133	benign	Gorlin syndrome	2023-07-07	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000245867	SCV001927280	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000245867	SCV001957256	benign	not specified		no assertion criteria provided	clinical testing