Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Division of Medical Genetics, |
RCV001250441 | SCV001424816 | pathogenic | Familial cancer of breast | 2019-04-15 | criteria provided, single submitter | clinical testing | The c.599T>C variant has been reported in the literature in large meta-analysis studies to result in an increased risk for breast cancer and colon cancer (OR ~1.5) (Liu 2012, Liu 2012, Han 2013). The c.599T>C variant has been reported in families with variable penetrance and incomplete segregation with disease (Roeb 2012). The c.599T>C variant has an overall allele frequency of 0.00154 in the Broad Institute ExAC Browser (http://exac.broadinstitute.org/), and is more common in individuals from Poland and Finland (Desrichard 2011, Lek 2016). Thus, this variant is interpreted as pathogenic, low-penetrance. |
| Invitae | RCV001250441 | SCV002286352 | uncertain significance | Familial cancer of breast | 2021-03-29 | 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 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"). This variant has been observed in individual(s) with pancreatic cancer (PMID: 31871297). ClinVar contains an entry for this variant (Variation ID: 973771). This variant is not present in population databases (ExAC no frequency). This sequence change replaces valine with alanine at codon 200 of the CHEK2 protein (p.Val200Ala). The valine residue is highly conserved and there is a small physicochemical difference between valine and alanine. |