ClinVar Miner

Submissions for variant NM_000245.4(MET):c.241G>T (p.Val81Phe)

gnomAD frequency: 0.00001  dbSNP: rs757883355
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002235020 SCV000947351 uncertain significance Renal cell carcinoma 2024-01-28 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 81 of the MET protein (p.Val81Phe). This variant is present in population databases (rs757883355, gnomAD 0.006%). 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: 651869). 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.
Ambry Genetics RCV002442700 SCV002732860 uncertain significance Hereditary cancer-predisposing syndrome 2023-02-01 criteria provided, single submitter clinical testing The p.V81F variant (also known as c.241G>T), located in coding exon 1 of the MET gene, results from a G to T substitution at nucleotide position 241. The valine at codon 81 is replaced by phenylalanine, an amino acid with highly similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
PreventionGenetics, part of Exact Sciences RCV003411783 SCV004116298 uncertain significance MET-related disorder 2022-12-05 criteria provided, single submitter clinical testing The MET c.241G>T variant is predicted to result in the amino acid substitution p.Val81Phe. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0065% of alleles in individuals of South Asian descent in gnomAD (http://gnomad.broadinstitute.org/variant/7-116339379-G-T) and is interpreted as uncertain significance in ClinVar (https://preview.ncbi.nlm.nih.gov/clinvar/variation/651869/). 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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