Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002034922 | SCV002111056 | uncertain significance | Retinoblastoma | 2023-02-14 | 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 missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The arginine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 1345099). This variant has not been reported in the literature in individuals affected with RB1-related conditions. This variant is present in population databases (rs750946437, gnomAD 0.003%). This sequence change replaces lysine, which is basic and polar, with arginine, which is basic and polar, at codon 925 of the RB1 protein (p.Lys925Arg). |
| Ambry Genetics | RCV003163999 | SCV003913081 | likely benign | Hereditary cancer-predisposing syndrome | 2023-03-02 | 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. |
| Baylor Genetics | RCV004571125 | SCV005054115 | uncertain significance | Malignant tumor of urinary bladder | 2024-03-15 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV004774473 | SCV005385027 | uncertain significance | not provided | 2024-02-20 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |