Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000797773 | SCV000937352 | uncertain significance | Retinoblastoma | 2018-09-03 | 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but 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. This variant is not present in population databases (ExAC no frequency). This sequence change replaces aspartic acid with alanine at codon 346 of the RB1 protein (p.Asp346Ala). The aspartic acid residue is highly conserved and there is a moderate physicochemical difference between aspartic acid and alanine. |
| Ambry Genetics | RCV002388454 | SCV002701544 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-01-04 | criteria provided, single submitter | clinical testing | The p.D346A variant (also known as c.1037A>C), located in coding exon 10 of the RB1 gene, results from an A to C substitution at nucleotide position 1037. The aspartic acid at codon 346 is replaced by alanine, an amino acid with dissimilar properties. This amino acid position is well 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. |