Submissions for variant NM_000245.4(MET):c.2908C>T (p.Arg970Cys)

gnomAD frequency: 0.00327  dbSNP: rs34589476

Total submissions: 24

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV001507128	SCV000166421	benign	Renal cell carcinoma	2024-02-01	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000131706	SCV000186744	likely benign	Hereditary cancer-predisposing syndrome	2018-09-27	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.
Illumina Laboratory Services, Illumina	RCV000123119	SCV000466454	benign	Papillary renal cell carcinoma type 1	2018-03-06	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.
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	RCV000034528	SCV000510820	likely benign	not provided	2017-01-24	criteria provided, single submitter	clinical testing	Converted during submission to Likely benign.
GeneDx	RCV000034528	SCV000567989	benign	not provided	2019-08-08	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 17322284, 17053076, 20670955, 25314153, 20368753, 23401458, 22128285, 25231402, 16734685, 25992381, 27626278, 28085233, 27636102, no PMID, 29970518, 14559814, 24728327, 23449277, 16189274, 15592501, 21847116, 15735036, 19723643, 26097886, 18564920, 22703879, 17404109, 23640142, 20370683, 20139696, 19037978, 18340114, 19318576, 17288874, 19861919, 17483355, 23662036, 19333071, 18709663, 20462834, 22838389, 20489150, 19393836, 21918175, 22530990, 25868855, 24327519, 24105670, 25416047, 24929890, 22973954, 26574927, 27153395, 28648934, 28116210, 27741505, 27899992, 28247034, 27013592, 28061464, 26934580, 27376238, 28603720, 28740441, 27923392, 28476232, 28619094, 31004003)
Mendelics	RCV000123119	SCV000838267	likely benign	Papillary renal cell carcinoma type 1	2018-07-02	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000034528	SCV000885699	likely benign	not provided	2023-11-09	criteria provided, single submitter	clinical testing
Institute of Human Genetics, University of Leipzig Medical Center	RCV000123119	SCV001440109	likely benign	Papillary renal cell carcinoma type 1	2019-01-01	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000034528	SCV001500458	likely benign	not provided	2024-07-01	criteria provided, single submitter	clinical testing	MET: BS2
Genetic Services Laboratory, University of Chicago	RCV000121339	SCV002069848	benign	not specified	2021-05-04	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000131706	SCV002532139	benign	Hereditary cancer-predisposing syndrome	2020-10-23	criteria provided, single submitter	curation
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV000121339	SCV002550810	likely benign	not specified	2024-07-31	criteria provided, single submitter	clinical testing
Genetics and Molecular Pathology, SA Pathology	RCV000123119	SCV002761777	benign	Papillary renal cell carcinoma type 1	2022-01-21	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003914903	SCV004728718	likely benign	MET-related disorder	2019-11-07	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).
Biesecker Lab/Clinical Genomics Section, National Institutes of Health	RCV000034528	SCV000043314	benign	not provided	2023-10-06	no assertion criteria provided	research	BA1 based on allele frequency in NFE of 0.0050422 in gnomAD. PMID:20670955 variant lacks transforming ability.
ITMI	RCV000121339	SCV000085514	not provided	not specified	2013-09-19	no assertion provided	reference population
Eurofins Ntd Llc (ga)	RCV000034528	SCV000111369	uncertain significance	not provided	2015-02-18	flagged submission	clinical testing
Database of Curated Mutations (DoCM)	RCV000444296	SCV000505271	likely pathogenic	Neoplasm	2014-12-26	no assertion criteria provided	literature only
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000121339	SCV000539623	uncertain significance	not specified	2016-03-28	flagged submission	clinical testing	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Gene associated with cancers, and variant has been identified in large B-cell lymphoma, but also pretty high frequency in ExAC with 1 homozygote, reported in apparently healthy individuals, and there are conflicting reports about functional impact (most recent functional study says no impact)
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000034528	SCV001740506	likely benign	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000034528	SCV001808712	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000034528	SCV001924487	likely benign	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000034528	SCV001927554	likely benign	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000121339	SCV001958952	benign	not specified		no assertion criteria provided	clinical testing