Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000048274 | SCV000076287 | uncertain significance | Hereditary breast and ovarian cancer syndrome | 2019-12-01 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid with lysine at codon 1219 of the BRCA1 protein (p.Glu1219Lys). The glutamic acid residue is moderately conserved and there is a small physicochemical difference between glutamic acid and lysine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with BRCA1-related disease. It has been observed with a pathogenic variant in BRCA1 in an individual in the Breast Cancer Information Core database (PMID: 10923033). While it is unknown if these variants are on the same or opposite chromosomes, this observation suggests that the c.3655G>A variant is not a primary cause of disease. ClinVar contains an entry for this variant (Variation ID: 54956). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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. |
| Ambry Genetics | RCV000129819 | SCV000184633 | uncertain significance | Hereditary cancer-predisposing syndrome | 2014-02-07 | criteria provided, single submitter | clinical testing | Insufficient or conflicting evidence |
| Breast Cancer Information Core |
RCV000112148 | SCV000144826 | uncertain significance | Breast-ovarian cancer, familial 1 | 2004-02-20 | no assertion criteria provided | clinical testing |