Total submissions: 7
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000532694 | SCV000623380 | uncertain significance | Renal cell carcinoma | 2024-01-25 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 48 of the MET protein (p.Ala48Thr). This variant is present in population databases (rs374050750, gnomAD 0.01%). 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: 454188). 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 with a negative predictive value of 80%. 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 | RCV000569043 | SCV000673688 | likely benign | Hereditary cancer-predisposing syndrome | 2023-07-06 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |
Fulgent Genetics, |
RCV000764682 | SCV000895814 | uncertain significance | Osteofibrous dysplasia; Papillary renal cell carcinoma type 1; Hepatocellular carcinoma; Autosomal recessive nonsyndromic hearing loss 97 | 2018-10-31 | criteria provided, single submitter | clinical testing | |
Gene |
RCV001547448 | SCV001767155 | uncertain significance | not provided | 2024-10-07 | criteria provided, single submitter | clinical testing | In silico analysis indicates that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 22675565) |
Baylor Genetics | RCV003470697 | SCV004192456 | uncertain significance | Autosomal recessive nonsyndromic hearing loss 97 | 2023-10-22 | criteria provided, single submitter | clinical testing | |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV001547448 | SCV005622882 | uncertain significance | not provided | 2023-12-07 | criteria provided, single submitter | clinical testing | |
Prevention |
RCV004745439 | SCV005345091 | uncertain significance | MET-related disorder | 2024-05-09 | no assertion criteria provided | clinical testing | The MET c.142G>A variant is predicted to result in the amino acid substitution p.Ala48Thr. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.012% of alleles in individuals of European (Non-Finnish) descent in gnomAD and is interpreted as a variant of uncertain significance in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/454188/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |