ClinVar Miner

Submissions for variant NM_000245.4(MET):c.2248A>G (p.Thr750Ala)

dbSNP: rs1060503531
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002230647 SCV000553296 uncertain significance Renal cell carcinoma 2016-09-22 criteria provided, single submitter clinical testing This sequence change replaces threonine with alanine at codon 750 of the MET protein (p.Thr750Ala). The threonine residue is moderately conserved and there is a small physicochemical difference between threonine and alanine. In summary, this variant is a novel missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may alter RNA splicing, but this prediction has not been confirmed by published transcriptional studies. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a MET-related disease.
Ambry Genetics RCV002429547 SCV002728812 uncertain significance Hereditary cancer-predisposing syndrome 2020-04-17 criteria provided, single submitter clinical testing The p.T750A variant (also known as c.2248A>G), located in coding exon 8 of the MET gene, results from an A to G substitution at nucleotide position 2248. The threonine at codon 750 is replaced by alanine, an amino acid with 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.

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