Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001039369 | SCV001202899 | uncertain significance | Familial cancer of breast; Fanconi anemia complementation group J | 2022-05-18 | criteria provided, single submitter | clinical testing | This sequence change replaces asparagine, which is neutral and polar, with histidine, which is basic and polar, at codon 1061 of the BRIP1 protein (p.Asn1061His). This variant is present in population databases (rs778430337, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with BRIP1-related conditions. ClinVar contains an entry for this variant (Variation ID: 837927). 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 tolerated. 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 | RCV002320245 | SCV002609217 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-01-27 | criteria provided, single submitter | clinical testing | The p.N1061H variant (also known as c.3181A>C), located in coding exon 19 of the BRIP1 gene, results from an A to C substitution at nucleotide position 3181. The asparagine at codon 1061 is replaced by histidine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |