Total submissions: 7
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000164922 | SCV000215610 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-06-07 | criteria provided, single submitter | clinical testing | The p.A1293V variant (also known as c.3878C>T and 3997C>T), located in coding exon 9 of the BRCA1 gene, results from a C to T substitution at nucleotide position 3878. The alanine at codon 1293 is replaced by valine, an amino acid with similar properties. This alteration was identified in an individual from a hereditary breast and/or ovarian cancer cohort (Zuntini R et al. Front Genet 2018 Sep;9:378). 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 | RCV001339366 | SCV001533106 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2023-08-23 | 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: 55036). This missense change has been observed in individual(s) with clinical features of BRCA1-related conditions (PMID: 30254663). This variant is present in population databases (rs80357213, gnomAD 0.002%). This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1293 of the BRCA1 protein (p.Ala1293Val). |
University of Washington Department of Laboratory Medicine, |
RCV000164922 | SCV003849660 | 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). |
Sharing Clinical Reports Project |
RCV000077556 | SCV000109358 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 1 | 2009-08-19 | no assertion criteria provided | clinical testing | |
Breast Cancer Information Core |
RCV000077556 | SCV000144908 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 1 | 2002-05-29 | no assertion criteria provided | clinical testing | |
Department of Pathology and Laboratory Medicine, |
RCV001355516 | SCV001550428 | uncertain significance | not provided | no assertion criteria provided | clinical testing | ||
Department of Medical and Surgical Sciences, |
RCV000077556 | SCV004228354 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 1 | 2023-09-01 | no assertion criteria provided | clinical testing | PM2(Supporting)+PP4(Moderate)+BP1(Strong) according to ACMG/AMP classification guidelines specified for BRCA1 & BRCA2 (Classification Criteria V1.0.0 2023-09-08 - https://cspec.genome.network/cspec/ui/svi/affiliation/50087) (PMID: 38160042) |