Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000562664 | SCV000669288 | uncertain significance | Hereditary cancer-predisposing syndrome | 2017-06-08 | criteria provided, single submitter | clinical testing | The p.P388A variant (also known as c.1162C>G), located in coding exon 10 of the CHEK2 gene, results from a C to G substitution at nucleotide position 1162. The proline at codon 388 is replaced by alanine, an amino acid with highly 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 | RCV001858288 | SCV002165819 | uncertain significance | Familial cancer of breast | 2022-02-02 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (gnomAD no frequency). 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"). ClinVar contains an entry for this variant (Variation ID: 483391). This variant has not been reported in the literature in individuals affected with CHEK2-related conditions. This sequence change replaces proline, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 388 of the CHEK2 protein (p.Pro388Ala). |