ClinVar Miner

Submissions for variant NM_000245.4(MET):c.1625A>G (p.His542Arg)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV003328830 SCV004035408 uncertain significance not provided 2023-03-14 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Ambry Genetics RCV003377947 SCV004083122 uncertain significance Hereditary cancer-predisposing syndrome 2023-06-27 criteria provided, single submitter clinical testing The p.H542R variant (also known as c.1625A>G), located in coding exon 4 of the MET gene, results from an A to G substitution at nucleotide position 1625. The histidine at codon 542 is replaced by arginine, 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV003594649 SCV004267640 uncertain significance Renal cell carcinoma 2023-09-29 criteria provided, single submitter clinical testing 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. 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. This variant has not been reported in the literature in individuals affected with MET-related conditions. This variant is present in population databases (rs775183859, gnomAD 0.007%). This sequence change replaces histidine, which is basic and polar, with arginine, which is basic and polar, at codon 542 of the MET protein (p.His542Arg).

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