ClinVar Miner

Submissions for variant NM_000245.4(MET):c.1477G>C (p.Glu493Gln)

gnomAD frequency: 0.00001  dbSNP: rs965319455
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000628732 SCV000749638 uncertain significance Renal cell carcinoma 2022-10-04 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with glutamine, which is neutral and polar, at codon 493 of the MET protein (p.Glu493Gln). This variant is present in population databases (no rsID available, gnomAD no frequency). This variant has not been reported in the literature in individuals affected with MET-related conditions. ClinVar contains an entry for this variant (Variation ID: 524856). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The glutamine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Athena Diagnostics RCV000992304 SCV001144503 uncertain significance not provided 2019-03-04 criteria provided, single submitter clinical testing
Ambry Genetics RCV001011713 SCV001172068 uncertain significance Hereditary cancer-predisposing syndrome 2022-01-10 criteria provided, single submitter clinical testing The c.1477G>C (p.E493Q) alteration is located in exon 4 (coding exon 3) of the MET gene. This alteration results from a G to C substitution at nucleotide position 1477, causing the glutamic acid (E) at amino acid position 493 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
GeneDx RCV000992304 SCV003805504 uncertain significance not provided 2023-02-24 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Baylor Genetics RCV003465382 SCV004192492 uncertain significance Autosomal recessive nonsyndromic hearing loss 97 2023-10-02 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000992304 SCV004220051 uncertain significance not provided 2019-03-04 criteria provided, single submitter clinical testing To the best of our knowledge, this variant has not been reported in the published literature. The frequency of this variant in the general population, 0.000032 (1/31404 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is uninformative in the assessment of its pathogenicity. Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is benign. Based on the available information, we are unable to determine the clinical significance of this variant.
Breakthrough Genomics, Breakthrough Genomics RCV000992304 SCV005195605 uncertain significance not provided criteria provided, single submitter not provided
PreventionGenetics, part of Exact Sciences RCV004745510 SCV005354282 uncertain significance MET-related disorder 2024-07-02 no assertion criteria provided clinical testing The MET c.1477G>C variant is predicted to result in the amino acid substitution p.Glu493Gln. To our knowledge, this variant has not been reported in the literature. This variant is reported in one alleles of undefined subpopulation out of 31,404 total alleles in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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