Total submissions: 7
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000461312 | SCV000549409 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2023-10-03 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 341 of the BRCA1 protein (p.Asp341Asn). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with breast and/or ovarian cancer (PMID: 18273839). ClinVar contains an entry for this variant (Variation ID: 409364). 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. 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. |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000758783 | SCV000887618 | uncertain significance | not provided | 2022-10-04 | criteria provided, single submitter | clinical testing | It has not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org). In the published literature, the variant has been reported in families with breast or ovarian cancer (PMID: 18273839 (2008)). Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is benign. Based on the available information, we are unable to determine the clinical significance of this variant. |
Color Diagnostics, |
RCV000775726 | SCV000910149 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-06-22 | criteria provided, single submitter | clinical testing | |
Mendelics | RCV000989905 | SCV001140613 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 1 | 2019-05-28 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV000775726 | SCV001178053 | uncertain significance | Hereditary cancer-predisposing syndrome | 2018-07-22 | criteria provided, single submitter | clinical testing | The p.D341N variant (also known as c.1021G>A), located in coding exon 9 of the BRCA1 gene, results from a G to A substitution at nucleotide position 1021. The aspartic acid at codon 341 is replaced by asparagine, an amino acid with highly similar properties. This alteration has been detected in a cohort of French breast and/or ovarian cancer families (Anczuków O et al. Genes Chromosomes Cancer, 2008 May;47:418-26). 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. |
Gene |
RCV000758783 | SCV002575799 | uncertain significance | not provided | 2022-03-23 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; Also known as 1140G>A; This variant is associated with the following publications: (PMID: 10426999, 20215511, 15343273, 9926942, 9582019, 11521194) |
University of Washington Department of Laboratory Medicine, |
RCV000775726 | SCV003846225 | 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). |