Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002233915 | SCV000749682 | uncertain significance | Renal cell carcinoma | 2022-04-28 | criteria provided, single submitter | clinical testing | Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This sequence change replaces proline, which is neutral and non-polar, with histidine, which is basic and polar, at codon 44 of the MET protein (p.Pro44His). 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: 524896). 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 | RCV002385971 | SCV002689738 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-12-07 | criteria provided, single submitter | clinical testing | The p.P44H variant (also known as c.131C>A), located in coding exon 1 of the MET gene, results from a C to A substitution at nucleotide position 131. The proline at codon 44 is replaced by histidine, an amino acid with 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. |