Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000813005 | SCV000953338 | uncertain significance | Familial cancer of breast | 2022-11-23 | 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: 656556). This missense change has been observed in individual(s) with breast cancer (PMID: 27616075, 30303537). This variant is present in population databases (no rsID available, gnomAD 0.003%). This sequence change replaces valine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 335 of the CHEK2 protein (p.Val335Leu). |
| Ambry Genetics | RCV002397681 | SCV002709196 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-10-26 | criteria provided, single submitter | clinical testing | The p.V335L variant (also known as c.1003G>T), located in coding exon 8 of the CHEK2 gene, results from a G to T substitution at nucleotide position 1003. The valine at codon 335 is replaced by leucine, 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. |