ClinVar Miner

Submissions for variant NM_000245.4(MET):c.1019A>G (p.Asp340Gly) (rs200690492)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000034513 SCV000111359 uncertain significance not provided 2013-04-24 criteria provided, single submitter clinical testing
Invitae RCV000535028 SCV000623363 uncertain significance Renal cell carcinoma 2020-10-23 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with glycine at codon 340 of the MET protein (p.Asp340Gly). The aspartic acid residue is highly conserved and there is a moderate physicochemical difference between aspartic acid and glycine. This variant is present in population databases (rs200690492, ExAC 0.002%). This variant has not been reported in the literature in individuals with MET-related disease. ClinVar contains an entry for this variant (Variation ID: 41608). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: Deleterious; PolyPhen-2: Probably Damaging; Align-GVGD: Class C0). 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 RCV000562476 SCV000673761 uncertain significance Hereditary cancer-predisposing syndrome 2018-07-31 criteria provided, single submitter clinical testing The p.D340G variant (also known as c.1019A>G), located in coding exon 1 of the MET gene, results from an A to G substitution at nucleotide position 1019. The aspartic acid at codon 340 is replaced by glycine, an amino acid with similar properties. <span style="font-family:sans-serif,arial,verdana,trebuchet ms">This alteration was previously reported as a secondary finding in 1/571 individuals undergoing exome<span style="font-family:sans-serif,arial,verdana,trebuchet ms"> sequencing due to an atherosclerosis phenotype (Johnston et al. Am. J. Hum. Genet<span style="font-family:sans-serif,arial,verdana,trebuchet ms">. 2012 Jul; 91(1):97-108). 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.
Biesecker Lab/Clinical Genomics Section,National Institutes of Health RCV000034513 SCV000043297 variant of unknown significance not provided 2012-07-13 no assertion criteria provided research Converted during submission to Uncertain significance.

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