Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000218622 | SCV000276041 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-09-02 | criteria provided, single submitter | clinical testing | The p.T1196K variant (also known as c.3587C>A and 3706C>A), located in coding exon 9 of the BRCA1 gene, results from a C to A substitution at nucleotide position 3587. The threonine at codon 1196 is replaced by lysine, an amino acid with some similar properties. This alteration has been reported as a variant of unknown significance based on mammalian conservation and chemical characteristics of the amino acid substitution (Burk-Herrick A et al. Mamm Genome. 2006 Mar; 17(3):257-70). 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 | RCV001301253 | SCV001490417 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2022-07-05 | 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: 54925). This missense change has been observed in individual(s) with a personal or family history of breast and/or ovarian cancer (PMID: 9333265). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces threonine, which is neutral and polar, with lysine, which is basic and polar, at codon 1196 of the BRCA1 protein (p.Thr1196Lys). |
Gene |
RCV002460902 | SCV002757597 | uncertain significance | not provided | 2022-05-26 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; Also known as 3706C>A |
University of Washington Department of Laboratory Medicine, |
RCV000218622 | SCV003848348 | 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 |
RCV000112126 | SCV000144798 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 1 | 1997-02-15 | no assertion criteria provided | clinical testing |