Submissions for variant NM_000245.4(MET):c.467C>T (p.Ser156Leu)

gnomAD frequency: 0.00061  dbSNP: rs56311081

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001450089	SCV000166428	likely benign	Renal cell carcinoma	2024-01-24	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000123126	SCV000466426	benign	Papillary renal cell carcinoma type 1	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	RCV000572531	SCV000664713	likely benign	Hereditary cancer-predisposing syndrome	2018-11-21	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, 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.
Mendelics	RCV003492549	SCV000838236	likely benign	Hereditary cancer	2024-01-23	criteria provided, single submitter	clinical testing
GeneDx	RCV001557296	SCV001779031	uncertain significance	not provided	2024-06-14	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Observed in individuals with breast cancer in published literature (PMID: 35264596); This variant is associated with the following publications: (PMID: 29084058, 34513100, 29212164, 36431263, 37835473, 35264596)
Sema4, Sema4	RCV000572531	SCV002532170	likely benign	Hereditary cancer-predisposing syndrome	2021-03-18	criteria provided, single submitter	curation
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV002465527	SCV002760395	uncertain significance	not specified	2024-07-31	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003975093	SCV004789529	likely benign	MET-related disorder	2020-09-21	no assertion criteria provided	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).