Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000132367 | SCV000187457 | likely benign | Hereditary cancer-predisposing syndrome | 2024-09-05 | 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. |
Labcorp Genetics |
RCV000535828 | SCV000623366 | uncertain significance | Renal cell carcinoma | 2023-12-21 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 351 of the MET protein (p.Pro351Ala). This variant is not present in population databases (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: 142899). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on MET 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. |
Institute for Clinical Genetics, |
RCV003237743 | SCV002011115 | uncertain significance | not provided | 2021-11-03 | criteria provided, single submitter | clinical testing | |
Prevention |
RCV003975137 | SCV004792946 | uncertain significance | MET-related disorder | 2024-02-28 | no assertion criteria provided | clinical testing | The MET c.1051C>G variant is predicted to result in the amino acid substitution p.Pro351Ala. To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |