Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV001020521 | SCV001182010 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-05-22 | criteria provided, single submitter | clinical testing | The p.A1175T variant (also known as c.3523G>A), located in coding exon 9 of the BRCA1 gene, results from a G to A substitution at nucleotide position 3523. The alanine at codon 1175 is replaced by threonine, an amino acid with similar properties. This amino acid position is highly 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. |
Invitae | RCV001068024 | SCV001233111 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2021-10-03 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine with threonine at codon 1175 of the BRCA1 protein (p.Ala1175Thr). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and threonine. 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: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals affected with BRCA1-related conditions. This variant is not present in population databases (ExAC no frequency). |
University of Washington Department of Laboratory Medicine, |
RCV001020521 | SCV003851756 | likely benign | Hereditary cancer-predisposing syndrome | 2023-03-23 | criteria provided, single submitter | curation | Missense variant in a coldspot region where missense variants are very unlikely to be pathogenic (PMID:31911673). |