Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000164262 | SCV000214887 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-05-01 | criteria provided, single submitter | clinical testing | The p.I816R variant (also known as c.2447T>G), located in coding exon 10 of the MET gene, results from a T to G substitution at nucleotide position 2447. The isoleucine at codon 816 is replaced by arginine, an amino acid with similar properties. This amino acid position is well 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. |
Labcorp Genetics |
RCV000701943 | SCV000830769 | uncertain significance | Renal cell carcinoma | 2023-07-19 | criteria provided, single submitter | clinical testing | 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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. ClinVar contains an entry for this variant (Variation ID: 184921). This variant has not been reported in the literature in individuals affected with MET-related conditions. This variant is present in population databases (rs764960693, gnomAD 0.004%). This sequence change replaces isoleucine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 816 of the MET protein (p.Ile816Arg). |