Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000572438 | SCV000661113 | uncertain significance | Hereditary cancer-predisposing syndrome | 2017-02-03 | criteria provided, single submitter | clinical testing | The p.E914K variant (also known as c.2740G>A), located in coding exon 9 of the BRCA1 gene, results from a G to A substitution at nucleotide position 2740. The glutamic acid at codon 914 is replaced by lysine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
University of Washington Department of Laboratory Medicine, |
RCV000572438 | SCV003849386 | 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). |
Color Diagnostics, |
RCV000572438 | SCV004360259 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-10-11 | criteria provided, single submitter | clinical testing | This missense variant replaces glutamic acid with lysine at codon 914 of the BRCA1 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |