Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001221139 | SCV001393165 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2020-09-09 | criteria provided, single submitter | clinical testing | This sequence change replaces histidine with leucine at codon 1197 of the BRCA1 protein (p.His1197Leu). The histidine residue is weakly conserved and there is a moderate physicochemical difference between histidine and leucine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with BRCA1-related conditions. 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, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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 | RCV002451511 | SCV002615234 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-02-06 | criteria provided, single submitter | clinical testing | The p.H1197L variant (also known as c.3590A>T), located in coding exon 9 of the BRCA1 gene, results from an A to T substitution at nucleotide position 3590. The histidine at codon 1197 is replaced by leucine, an amino acid with similar properties. This amino acid position is poorly 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. |
University of Washington Department of Laboratory Medicine, |
RCV002451511 | SCV003848325 | 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). |