Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002028601 | SCV002284030 | uncertain significance | Retinoblastoma | 2021-09-12 | 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 disruptive, 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 conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces serine with cysteine at codon 646 of the RB1 protein (p.Ser646Cys). The serine residue is highly conserved and there is a moderate physicochemical difference between serine and cysteine. |
| Ambry Genetics | RCV002407263 | SCV002719262 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-04-15 | criteria provided, single submitter | clinical testing | The p.S646C variant (also known as c.1937C>G), located in coding exon 19 of the RB1 gene, results from a C to G substitution at nucleotide position 1937. The serine at codon 646 is replaced by cysteine, an amino acid with dissimilar properties. This amino acid position is highly conserved in available vertebrate species. 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. |