ClinVar Miner

Submissions for variant NM_000245.4(MET):c.623A>G (p.Asp208Gly)

gnomAD frequency: 0.00002  dbSNP: rs587782086
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000130588 SCV000185461 uncertain significance Hereditary cancer-predisposing syndrome 2022-09-26 criteria provided, single submitter clinical testing The p.D208G variant (also known as c.623A>G), located in coding exon 1 of the MET gene, results from an A to G substitution at nucleotide position 623. The aspartic acid at codon 208 is replaced by glycine, an amino acid with similar properties. Based on protein sequence alignment, 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 p.D208G remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV001223449 SCV001395599 uncertain significance Renal cell carcinoma 2022-09-10 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 208 of the MET protein (p.Asp208Gly). This variant is present in population databases (rs587782086, gnomAD 0.003%). 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: 141889). 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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.
GeneDx RCV001775623 SCV002013978 uncertain significance not provided 2024-01-08 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; Observed in an individual with a primary pleural synovial sarcoma (Vatsayan et al., 2019. doi:10.4103/ijmpo.ijmpo_233_17)

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.