ClinVar Miner

Submissions for variant NM_000245.4(MET):c.3950T>A (p.Leu1317Gln)

gnomAD frequency: 0.00001  dbSNP: rs1159812687
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002231672 SCV000623445 uncertain significance Renal cell carcinoma 2017-02-02 criteria provided, single submitter clinical testing 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 missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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. This sequence change replaces leucine with glutamine at codon 1335 of the MET protein (p.Leu1335Gln). The leucine residue is moderately conserved and there is a moderate physicochemical difference between leucine and glutamine.
Ambry Genetics RCV001021644 SCV001183286 uncertain significance Hereditary cancer-predisposing syndrome 2024-12-03 criteria provided, single submitter clinical testing The p.L1335Q variant (also known as c.4004T>A), located in coding exon 20 of the MET gene, results from a T to A substitution at nucleotide position 4004. The leucine at codon 1335 is replaced by glutamine, an amino acid with dissimilar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear.
GeneDx RCV001775840 SCV002013827 uncertain significance not provided 2024-02-20 criteria provided, single submitter clinical testing Not observed at a significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge

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