ClinVar Miner

Submissions for variant NM_000245.4(MET):c.1862C>T (p.Thr621Ile)

gnomAD frequency: 0.00007  dbSNP: rs375951814
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000628759 SCV000749665 uncertain significance Renal cell carcinoma 2024-01-27 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 621 of the MET protein (p.Thr621Ile). This variant is present in population databases (rs375951814, gnomAD 0.007%). 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: 524880). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The isoleucine 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.
Ambry Genetics RCV001013433 SCV001174016 likely benign Hereditary cancer-predisposing syndrome 2023-01-26 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 RCV001756034 SCV002007376 uncertain significance not provided 2024-11-06 criteria provided, single submitter clinical testing In silico analysis indicates that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden RCV001756034 SCV002011113 uncertain significance not provided 2021-11-03 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV002483765 SCV002788780 uncertain significance Osteofibrous dysplasia; Papillary renal cell carcinoma type 1; Hepatocellular carcinoma; Autosomal recessive nonsyndromic hearing loss 97 2021-08-04 criteria provided, single submitter clinical testing
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital RCV004596305 SCV005090769 uncertain significance not specified 2024-07-31 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV001756034 SCV005622892 uncertain significance not provided 2024-04-15 criteria provided, single submitter clinical testing

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