Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV002013838 | SCV002307462 | uncertain significance | Retinoblastoma | 2022-11-16 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 48 of the RB1 protein (p.Glu48Gly). This variant has not been reported in the literature in individuals affected with RB1-related conditions. 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. ClinVar contains an entry for this variant (Variation ID: 1508233). |
Ambry Genetics | RCV002389027 | SCV002699334 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-07-15 | criteria provided, single submitter | clinical testing | The p.E48G variant (also known as c.143A>G), located in coding exon 2 of the RB1 gene, results from an A to G substitution at nucleotide position 143. The glutamic acid at codon 48 is replaced by glycine, an amino acid with similar properties. This amino acid position is conserved. 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. |