Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV001024087 | SCV001186045 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2019-09-05 | criteria provided, single submitter | clinical testing | The p.V1809D variant (also known as c.5426T>A), located in coding exon 21 of the BRCA1 gene, results from a T to A substitution at nucleotide position 5426. The valine at codon 1809 is replaced by aspartic acid, an amino acid with highly dissimilar properties. One functional study found that this nucleotide substitution is deleterious in a high throughput genome editing haploid cell survival assay (Findlay GM et al. Nature. 2018 10;562:217-222). Based on internal structural analysis, p.V1809D is highly disruptive to this region of BRCA1 (Ambry internal data; Gaiser OJ et al. Biochemistry. 2004 Dec;43(51):15983-95). This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the majority of available evidence to date, this variant is likely to be pathogenic. |
Brotman Baty Institute, |
RCV001072912 | SCV001238374 | not provided | Breast-ovarian cancer, familial, susceptibility to, 1 | no assertion provided | in vitro |