Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000123114 | SCV000166416 | uncertain significance | Renal cell carcinoma | 2024-01-19 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 504 of the MET protein (p.Val504Phe). This variant is present in population databases (rs587780735, gnomAD 0.003%). 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: 135961). 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 | RCV001011970 | SCV001172363 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-03-18 | criteria provided, single submitter | clinical testing | The p.V504F variant (also known as c.1510G>T), located in coding exon 3 of the MET gene, results from a G to T substitution at nucleotide position 1510. The valine at codon 504 is replaced by phenylalanine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Gene |
RCV001569039 | SCV001793020 | uncertain significance | not provided | 2024-08-07 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); 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: 30709382) |
Baylor Genetics | RCV004567064 | SCV005057842 | uncertain significance | Autosomal recessive nonsyndromic hearing loss 97 | 2024-03-11 | criteria provided, single submitter | clinical testing | |
Fulgent Genetics, |
RCV005031632 | SCV005673762 | uncertain significance | Osteofibrous dysplasia; Papillary renal cell carcinoma type 1; Hepatocellular carcinoma; Autosomal recessive nonsyndromic hearing loss 97; Arthrogryposis, distal, IIa 11 | 2024-03-07 | criteria provided, single submitter | clinical testing |