Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002398923 | SCV002714698 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-04-05 | criteria provided, single submitter | clinical testing | The p.D571V variant (also known as c.1712A>T), located in coding exon 18 of the RB1 gene, results from an A to T substitution at nucleotide position 1712. The aspartic acid at codon 571 is replaced by valine, an amino acid with highly dissimilar properties. This amino acid position is conserved. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Labcorp Genetics |
RCV003514578 | SCV004335280 | uncertain significance | Retinoblastoma | 2023-10-22 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with valine, which is neutral and non-polar, at codon 571 of the RB1 protein (p.Asp571Val). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with RB1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1778584). 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 RB1 protein function. 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. |