Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Illumina Laboratory Services, |
RCV001162953 | SCV001324949 | uncertain significance | Papillary renal cell carcinoma type 1 | 2018-01-13 | criteria provided, single submitter | clinical testing | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. |
| Labcorp Genetics |
RCV001882518 | SCV002318287 | uncertain significance | Renal cell carcinoma | 2021-09-24 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid with aspartic acid at codon 1100 of the MET protein (p.Glu1100Asp). The glutamic acid residue is moderately conserved and there is a small physicochemical difference between glutamic acid and aspartic acid. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with MET-related conditions. 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: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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 | RCV002320383 | SCV002611239 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-05-01 | criteria provided, single submitter | clinical testing | The p.E1100D variant (also known as c.3300A>T), located in coding exon 14 of the MET gene, results from an A to T substitution at nucleotide position 3300. The glutamic acid at codon 1100 is replaced by aspartic acid, an amino acid with highly similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Revvity Omics, |
RCV003490093 | SCV004236347 | uncertain significance | not provided | 2023-05-08 | criteria provided, single submitter | clinical testing |