Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000203872 | SCV000261357 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2021-10-14 | 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 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"). ClinVar contains an entry for this variant (Variation ID: 220648). 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). This sequence change replaces lysine with asparagine at codon 947 of the BRCA1 protein (p.Lys947Asn). The lysine residue is moderately conserved and there is a moderate physicochemical difference between lysine and asparagine. |
Ambry Genetics | RCV000223008 | SCV000274067 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-10-21 | criteria provided, single submitter | clinical testing | The p.K947N variant (also known as c.2841A>T), located in coding exon 9 of the BRCA1 gene, results from an A to T substitution at nucleotide position 2841. The lysine at codon 947 is replaced by asparagine, an amino acid with similar properties. This amino acid position is not 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. |
University of Washington Department of Laboratory Medicine, |
RCV000223008 | SCV003849311 | 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). |