Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000223347 | SCV000274190 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-04-19 | criteria provided, single submitter | clinical testing | The p.D411N variant (also known as c.1231G>A), located in coding exon 9 of the BRCA1 gene, results from a G to A substitution at nucleotide position 1231. The aspartic acid at codon 411 is replaced by asparagine, an amino acid with highly similar properties. In one study, this alteration was reported to be neutral based on results from a prediction model that uses evolutionary conservation scores (Abkevich et al. J Med Genet. 2004; 41:492–507). In another study, this alteration was predicted to be conferring low oncogenic risk based on a prediction model that also uses evolutionary conservation scores (Burk-Herrick et al. Mammalian Genome. 2006; 17:257-270). 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. |
Invitae | RCV001342656 | SCV001536600 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2022-08-22 | 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt BRCA1 protein function. ClinVar contains an entry for this variant (Variation ID: 54168). This variant has not been reported in the literature in individuals affected with BRCA1-related conditions. This variant is present in population databases (rs80357301, gnomAD 0.0009%). This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 411 of the BRCA1 protein (p.Asp411Asn). |
University of Washington Department of Laboratory Medicine, |
RCV000223347 | SCV003846087 | 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). |
Breast Cancer Information Core |
RCV000111569 | SCV000144034 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 1 | 2002-05-29 | no assertion criteria provided | clinical testing |