Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000551740 | SCV000629327 | uncertain significance | Retinoblastoma | 2020-01-23 | criteria provided, single submitter | clinical testing | In summary, this variant is a novel missense change with uncertain impact on protein function. 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. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a RB1-related disease. This sequence change replaces glutamic acid with alanine at codon 119 of the RB1 protein (p.Glu119Ala). The glutamic acid residue is highly conserved and there is a moderate physicochemical difference between glutamic acid and alanine. |
| Ambry Genetics | RCV002456070 | SCV002613150 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-09-24 | criteria provided, single submitter | clinical testing | The p.E119A variant (also known as c.356A>C), located in coding exon 3 of the RB1 gene, results from an A to C substitution at nucleotide position 356. The glutamic acid at codon 119 is replaced by alanine, an amino acid with dissimilar 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. |