Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV001012966 | SCV001173493 | uncertain significance | Hereditary cancer-predisposing syndrome | 2018-09-11 | criteria provided, single submitter | clinical testing | The p.K583E variant (also known as c.1747A>G), located in coding exon 11 of the RAD50 gene, results from an A to G substitution at nucleotide position 1747. The lysine at codon 583 is replaced by glutamic acid, an amino acid with similar 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. |
Invitae | RCV001012966 | SCV002229715 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-07-15 | 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 819979). This variant has not been reported in the literature in individuals affected with RAD50-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces lysine with glutamic acid at codon 583 of the RAD50 protein (p.Lys583Glu). The lysine residue is moderately conserved and there is a small physicochemical difference between lysine and glutamic acid. |