Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001930888 | SCV002196093 | uncertain significance | Retinoblastoma | 2021-02-22 | 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). This variant has not been reported in the literature in individuals with RB1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces aspartic acid with asparagine at codon 604 of the RB1 protein (p.Asp604Asn). The aspartic acid residue is highly conserved and there is a small physicochemical difference between aspartic acid and asparagine. |
| Ambry Genetics | RCV002407081 | SCV002711944 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-06-20 | criteria provided, single submitter | clinical testing | The p.D604N variant (also known as c.1810G>A), located in coding exon 18 of the RB1 gene, results from a G to A substitution at nucleotide position 1810. The aspartic acid at codon 604 is replaced by asparagine, an amino acid with highly 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. |