ClinVar Miner

Submissions for variant NM_000245.4(MET):c.3356G>C (p.Gly1119Ala)

gnomAD frequency: 0.00003  dbSNP: rs201037977
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000569927 SCV000673711 likely benign Hereditary cancer-predisposing syndrome 2018-09-29 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 RCV001328503 SCV000826144 uncertain significance Renal cell carcinoma 2024-01-20 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 1137 of the MET protein (p.Gly1137Ala). This variant is present in population databases (rs201037977, gnomAD 0.009%). This missense change has been observed in individual(s) with breast cancer (PMID: 35264596). ClinVar contains an entry for this variant (Variation ID: 41625). 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 with a negative predictive value of 80%. 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.
Mendelics RCV000697527 SCV000838273 uncertain significance Papillary renal cell carcinoma type 1 2018-07-02 criteria provided, single submitter clinical testing
GeneDx RCV000034530 SCV001794412 uncertain significance not provided 2023-11-26 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant does not alter protein structure/function; Observed in individuals with breast or colorectal cancer (PMID: 29684080, 35264596); This variant is associated with the following publications: (PMID: 21774103, 22703879, 29684080, 35264596)
Baylor Genetics RCV003460544 SCV004192513 uncertain significance Autosomal recessive nonsyndromic hearing loss 97 2024-03-25 criteria provided, single submitter clinical testing
Biesecker Lab/Clinical Genomics Section, National Institutes of Health RCV000034530 SCV000043318 variant of unknown significance not provided 2012-07-13 no assertion criteria provided research Converted during submission to Uncertain significance.

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