Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000533050 | SCV000633539 | uncertain significance | Familial cancer of breast; Fanconi anemia complementation group J | 2022-05-08 | 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 461064). This variant has not been reported in the literature in individuals affected with BRIP1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 395 of the BRIP1 protein (p.Ala395Val). |
Ambry Genetics | RCV001010086 | SCV001170234 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-05-24 | criteria provided, single submitter | clinical testing | The p.A395V variant (also known as c.1184C>T), located in coding exon 8 of the BRIP1 gene, results from a C to T substitution at nucleotide position 1184. The alanine at codon 395 is replaced by valine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. This alteration was identified in 1/6341 breast cancer patients, 0/706 ovarian cancer patients, and 1/2189 matched controls (Weber-Lassalle N et al. Breast Cancer Res., 2018 Jan;20:7). In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Institute of Human Genetics, |
RCV001262879 | SCV001440913 | uncertain significance | Familial cancer of breast | 2019-01-01 | criteria provided, single submitter | clinical testing |