Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000565429 | SCV000663601 | uncertain significance | Hereditary cancer-predisposing syndrome | 2016-03-01 | criteria provided, single submitter | clinical testing | The p.E290K variant (also known as c.868G>A), located in coding exon 6 of the RAD50 gene, results from a G to A substitution at nucleotide position 868. The glutamic acid at codon 290 is replaced by lysine, an amino acid with similar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6501 samples (13002 alleles) with coverage at this position. To date, this alteration has been detected with an allele frequency of approximately 0.002% (greater than 120000 alleles tested) in our clinical cohort. This amino acid position is not 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 p.E290K remains unclear. |
Invitae | RCV000565429 | SCV002306247 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-09-29 | 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: 480389). 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 glutamic acid with lysine at codon 290 of the RAD50 protein (p.Glu290Lys). The glutamic acid residue is moderately conserved and there is a small physicochemical difference between glutamic acid and lysine. |