Submissions for variant NM_000245.4(MET):c.1039G>A (p.Ala347Thr)

gnomAD frequency: 0.00068  dbSNP: rs200074800

Total submissions: 12

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV001420970	SCV000153830	likely benign	Renal cell carcinoma	2024-02-01	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000119117	SCV000466434	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.
GeneDx	RCV000657129	SCV000569718	uncertain significance	not provided	2023-04-17	criteria provided, single submitter	clinical testing	Published functional studies demonstrate the variant to have similar hepatocyte growth factor ligand binding as the wild type protein (Krishnaswamy et al., 2009); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 24728327, 26681766, 33420229, 24465403, 20139696, 25801821, 24983367, 24082139, 21904579, 28873162, 24755471, 19723643, 35441217)
Ambry Genetics	RCV000567774	SCV000673685	likely benign	Hereditary cancer-predisposing syndrome	2018-10-05	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.
Mendelics	RCV003492511	SCV000838244	likely benign	Hereditary cancer	2024-01-23	criteria provided, single submitter	clinical testing
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden	RCV000657129	SCV002011116	uncertain significance	not provided	2021-11-03	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000121345	SCV002068320	likely benign	not specified	2021-03-06	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000567774	SCV002532088	likely benign	Hereditary cancer-predisposing syndrome	2021-06-28	criteria provided, single submitter	curation
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV000121345	SCV002550778	uncertain significance	not specified	2024-02-06	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV003467064	SCV004192458	uncertain significance	Autosomal recessive nonsyndromic hearing loss 97	2023-10-20	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003894956	SCV004708798	likely benign	MET-related condition	2019-09-25	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).
ITMI	RCV000121345	SCV000085522	not provided	not specified	2013-09-19	no assertion provided	reference population