ClinVar Miner

Submissions for variant NM_000245.4(MET):c.3521A>G (p.His1174Arg)

gnomAD frequency: 0.00041  dbSNP: rs372830789
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000195706 SCV000254686 likely benign Renal cell carcinoma 2024-01-21 criteria provided, single submitter clinical testing
Ambry Genetics RCV000564694 SCV000673727 likely benign Hereditary cancer-predisposing syndrome 2020-06-25 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.
GeneDx RCV001566274 SCV001789770 uncertain significance not provided 2022-08-12 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant does not alter protein structure/function; Observed in an individual with neuroblastoma (Zhang et al., 2015); This variant is associated with the following publications: (PMID: 26580448)
Genetic Services Laboratory, University of Chicago RCV003150976 SCV003839712 uncertain significance not specified 2022-07-27 no assertion criteria provided clinical testing DNA sequence analysis of the MET gene demonstrated a sequence change, c.3575A>G, in exon 17 that results in an amino acid change, p.His1192Arg. This sequence change does not appear to have been previously described in individuals with MET-related disorders. This sequence change has been described in the gnomAD database with a frequency of 0.11% in the African subpopulation (dbSNP rs372830789). The p.His1192Arg change affects a highly conserved amino acid residue located in a domain of the MET protein that is known to be functional. In-silico pathogenicity prediction tools (SIFT, PolyPhen2, Align GVGD, REVEL) provide contradictory results for the p.His1192Arg substitution. Due to insufficient evidences and the lack of functional studies, the clinical significance of the p.His1192Arg change remains unknown at this time. Heterozygous pathogenic variants in MET are associated with papillary renal cell carcinoma [OMIM# 605074].
PreventionGenetics, part of Exact Sciences RCV004745272 SCV005359829 likely benign MET-related disorder 2024-05-12 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).

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