ClinVar Miner

Submissions for variant NM_000245.4(MET):c.1484C>G (p.Thr495Arg)

dbSNP: rs45585831
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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 RCV001328504 SCV000294263 uncertain significance Renal cell carcinoma 2024-01-17 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with arginine, which is basic and polar, at codon 495 of the MET protein (p.Thr495Arg). This variant is present in population databases (rs45585831, gnomAD 0.006%). This missense change has been observed in individual(s) with parathyroid cancer (PMID: 30093976). ClinVar contains an entry for this variant (Variation ID: 246625). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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.
Illumina Laboratory Services, Illumina RCV000236379 SCV000466442 uncertain significance 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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Ambry Genetics RCV000568824 SCV000673754 likely benign Hereditary cancer-predisposing syndrome 2024-04-12 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 RCV001785527 SCV002028009 uncertain significance not provided 2022-08-05 criteria provided, single submitter clinical testing Not observed at a significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Observed in an individual with parathyroid cancer (Chan et al., 2018); This variant is associated with the following publications: (PMID: 30093976)
Baylor Genetics RCV003463705 SCV004192478 uncertain significance Autosomal recessive nonsyndromic hearing loss 97 2023-10-10 criteria provided, single submitter clinical testing

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