Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000566863 | SCV000661736 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-09-01 | criteria provided, single submitter | clinical testing | The p.N185K variant (also known as c.555C>G), located in coding exon 3 of the CHEK2 gene, results from a C to G substitution at nucleotide position 555. The asparagine at codon 185 is replaced by lysine, an amino acid with similar properties. This alteration behaved as semi-functional in an in vivo, yeast-based growth rate assay (Delimitsou A et al. Hum Mutat, 2019 05;40:631-648). 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 | RCV001865715 | SCV002201435 | uncertain significance | Familial cancer of breast | 2022-08-31 | criteria provided, single submitter | clinical testing | This sequence change replaces asparagine, which is neutral and polar, with lysine, which is basic and polar, at codon 185 of the CHEK2 protein (p.Asn185Lys). This variant is present in population databases (rs780782542, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with CHEK2-related conditions. ClinVar contains an entry for this variant (Variation ID: 479555). 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: "Probably Damaging"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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. |