ClinVar Miner

Submissions for variant NM_000245.4(MET):c.840G>T (p.Arg280Ser)

gnomAD frequency: 0.00001  dbSNP: rs1207381066
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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 RCV000561905 SCV000673764 uncertain significance Hereditary cancer-predisposing syndrome 2024-06-28 criteria provided, single submitter clinical testing The p.R280S variant (also known as c.840G>T), located in coding exon 1 of the MET gene, results from a G to T substitution at nucleotide position 840. The arginine at codon 280 is replaced by serine, an amino acid with dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
GeneDx RCV001775898 SCV002013864 uncertain significance not provided 2019-10-10 criteria provided, single submitter clinical testing Not observed in large population cohorts (Lek 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge
Labcorp Genetics (formerly Invitae), Labcorp RCV001853776 SCV002265005 uncertain significance Renal cell carcinoma 2023-12-17 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with serine, which is neutral and polar, at codon 280 of the MET protein (p.Arg280Ser). This variant is not present in population databases (gnomAD no frequency). 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: 485748). 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 expected to disrupt MET protein function with a positive 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.
Baylor Genetics RCV004569278 SCV005057875 uncertain significance Autosomal recessive nonsyndromic hearing loss 97 2024-02-05 criteria provided, single submitter clinical testing

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