Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000220616 | SCV000276943 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-11-04 | criteria provided, single submitter | clinical testing | The p.T710A variant (also known as c.2128A>G), located in coding exon 9 of the BRCA1 gene, results from an A to G substitution at nucleotide position 2128. The threonine at codon 710 is replaced by alanine, an amino acid with similar properties. In one study, this alteration was seen in 1 of 7400 Czech high risk breast and/or ovarian cancer families (Machackova E et al. Klin Onkol, 2019;32:51-71). This amino acid position is 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. |
| Invitae | RCV000800757 | SCV000940488 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2018-12-01 | 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 output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The alanine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with BRCA1-related conditions. ClinVar contains an entry for this variant (Variation ID: 232737). This variant is not present in population databases (ExAC no frequency). This sequence change replaces threonine with alanine at codon 710 of the BRCA1 protein (p.Thr710Ala). The threonine residue is moderately conserved and there is a small physicochemical difference between threonine and alanine. |
| University of Washington Department of Laboratory Medicine, |
RCV000220616 | SCV003849477 | 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). |