Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV001025208 | SCV001187352 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-03-30 | criteria provided, single submitter | clinical testing | The p.P213H variant (also known as c.638C>A), located in coding exon 4 of the CHEK2 gene, results from a C to A substitution at nucleotide position 638. The proline at codon 213 is replaced by histidine, an amino acid with similar properties. This alteration has been reported with a carrier frequency of 0 in 7051 unselected breast cancer patients and 0.00062 in 11241 female controls of Japanese ancestry (Momozawa Y et al. Nat Commun, 2018 10;9:4083). This amino acid position is highly 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 | RCV001070326 | SCV001235548 | uncertain significance | Familial cancer of breast | 2022-02-14 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 826374). This variant has not been reported in the literature in individuals affected with CHEK2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces proline, which is neutral and non-polar, with histidine, which is basic and polar, at codon 213 of the CHEK2 protein (p.Pro213His). 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: "Probably Damaging"; Align-GVGD: "Class C0"). |