Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001016789 | SCV001177786 | likely benign | Hereditary cancer-predisposing syndrome | 2023-02-07 | 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 |
RCV001050355 | SCV001214456 | uncertain significance | Renal cell carcinoma | 2024-01-12 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 952 of the MET protein (p.Leu952Phe). This variant is present in population databases (no rsID available, gnomAD 0.002%). 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: 821903). 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. |
| Gene |
RCV002274116 | SCV002559650 | uncertain significance | not provided | 2024-06-10 | criteria provided, single submitter | clinical testing | Not observed at 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 |
| Baylor Genetics | RCV003467632 | SCV004192480 | uncertain significance | Autosomal recessive nonsyndromic hearing loss 97 | 2023-10-09 | criteria provided, single submitter | clinical testing | |
| Prevention |
RCV003973029 | SCV004799448 | uncertain significance | MET-related disorder | 2024-01-22 | no assertion criteria provided | clinical testing | The MET c.2856G>C variant is predicted to result in the amino acid substitution p.Leu952Phe. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0016% of alleles in individuals of European (Non-Finnish) descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |