Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000218712 | SCV000277558 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-09-27 | criteria provided, single submitter | clinical testing | The p.E5K variant (also known as c.13G>A), located in coding exon 1 of the RAD50 gene, results from a G to A substitution at nucleotide position 13. The glutamic acid at codon 5 is replaced by lysine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Invitae | RCV000218712 | SCV000830747 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-03-13 | 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. ClinVar contains an entry for this variant (Variation ID: 233223). This variant has not been reported in the literature in individuals affected with RAD50-related conditions. This variant is present in population databases (rs756334508, gnomAD 0.007%). This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 5 of the RAD50 protein (p.Glu5Lys). |