ClinVar Miner

Submissions for variant NM_000245.4(MET):c.1660G>A (p.Gly554Arg)

gnomAD frequency: 0.00001  dbSNP: rs200218511
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000167137 SCV000217967 likely benign Hereditary cancer-predisposing syndrome 2023-05-11 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV000536508 SCV000623386 uncertain significance Renal cell carcinoma 2022-10-27 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 554 of the MET protein (p.Gly554Arg). This variant is present in population databases (rs200218511, gnomAD 0.009%). 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: 134652). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt MET 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.
GeneDx RCV004719702 SCV005326177 uncertain significance not provided 2023-05-19 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Identified in healthy individuals undergoing whole genome sequencing (Bodian et al., 2014); This variant is associated with the following publications: (PMID: 24728327)
ITMI RCV000121351 SCV000085530 not provided not specified 2013-09-19 no assertion provided reference population

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