Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000632926 | SCV000754133 | uncertain significance | Retinoblastoma | 2020-04-09 | 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 create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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 serine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with RB1-related disease. ClinVar contains an entry for this variant (Variation ID: 527899). This variant is not present in population databases (ExAC no frequency). This sequence change replaces asparagine with serine at codon 480 of the RB1 protein (p.Asn480Ser). The asparagine residue is moderately conserved and there is a small physicochemical difference between asparagine and serine. |
| Prevention |
RCV003411501 | SCV004109032 | uncertain significance | RB1-related disorder | 2023-05-11 | criteria provided, single submitter | clinical testing | The RB1 c.1439A>G variant is predicted to result in the amino acid substitution p.Asn480Ser. To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. In ClinVar, this variant is listed as a variant of uncertain significance (https://www.ncbi.nlm.nih.gov/clinvar/variation/527899/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |
| Baylor Genetics | RCV003459510 | SCV004208534 | uncertain significance | Malignant tumor of urinary bladder | 2023-07-03 | criteria provided, single submitter | clinical testing |