Total submissions: 8
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000628732 | SCV000749638 | uncertain significance | Renal cell carcinoma | 2022-10-04 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid, which is acidic and polar, with glutamine, which is neutral and polar, at codon 493 of the MET protein (p.Glu493Gln). This variant is present in population databases (no rsID available, gnomAD no frequency). 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: 524856). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The glutamine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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. |
Athena Diagnostics | RCV000992304 | SCV001144503 | uncertain significance | not provided | 2019-03-04 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV001011713 | SCV001172068 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-01-10 | criteria provided, single submitter | clinical testing | The c.1477G>C (p.E493Q) alteration is located in exon 4 (coding exon 3) of the MET gene. This alteration results from a G to C substitution at nucleotide position 1477, causing the glutamic acid (E) at amino acid position 493 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
Gene |
RCV000992304 | SCV003805504 | uncertain significance | not provided | 2023-02-24 | 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 |
Baylor Genetics | RCV003465382 | SCV004192492 | uncertain significance | Autosomal recessive nonsyndromic hearing loss 97 | 2023-10-02 | criteria provided, single submitter | clinical testing | |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000992304 | SCV004220051 | uncertain significance | not provided | 2019-03-04 | criteria provided, single submitter | clinical testing | To the best of our knowledge, this variant has not been reported in the published literature. The frequency of this variant in the general population, 0.000032 (1/31404 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is uninformative in the assessment of its pathogenicity. Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is benign. Based on the available information, we are unable to determine the clinical significance of this variant. |
Breakthrough Genomics, |
RCV000992304 | SCV005195605 | uncertain significance | not provided | criteria provided, single submitter | not provided | ||
Prevention |
RCV004745510 | SCV005354282 | uncertain significance | MET-related disorder | 2024-07-02 | no assertion criteria provided | clinical testing | The MET c.1477G>C variant is predicted to result in the amino acid substitution p.Glu493Gln. To our knowledge, this variant has not been reported in the literature. This variant is reported in one alleles of undefined subpopulation out of 31,404 total alleles in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |