Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000509683 | SCV000608218 | uncertain significance | Hereditary cancer-predisposing syndrome | 2016-02-09 | criteria provided, single submitter | clinical testing | <span style="font-family:arial,helvetica,sans-serif"><span style="font-size:12px">The p.V1696L variant (also known as c.5086G>C), located in coding exon 16 of the BRCA1 gene, results from a G to C substitution at nucleotide position 5086. The valine at codon 1696 is replaced by leucine, an amino acid with highly similar properties. This variant is located in the BRCT domain of the BRCA1 protein, and functional studies indicate a moderate effect on <span style="background-color:rgb(255, 255, 255); color:rgb(51, 51, 51)">structural integrity and stability(Williams RS et al. J. Biol. Chem. 2003 Dec; 278(52):53007-16; Williams RS et al. Nat. Struct. Mol. Biol. 2004 Jun; 11(6):519-25; Glover JN, Fam. Cancer 2006; 5(1):89-93; Drikos I et al. Proteins 2009 Nov; 77(2):464-76; Lee MS et al. Cancer Res. 2010 Jun; 70(12):4880-90). This variant was previously reported in the SNPDatabase as rs80357125, but was absent from population-based cohorts in the NHLBI Exome Sequencing Project (ESP) and 1000 Genomes Project databases. To date, this variant has been detected with an allele frequency of approximately 0.0004% (greater than 225000 alleles tested) in our clinical cohort. This amino acid position is highly conserved in available vertebrate species. In addition, this variant is predicted to be benign and deleterious by PolyPhen and SIFT in silico analyses, respectively. Since supporting evidence is limited at this time, the clinical significance of this variant remains unclear.​ |
| Invitae | RCV002513664 | SCV003441931 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2023-09-28 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 1696 of the BRCA1 protein (p.Val1696Leu). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of BRCA1-related conditions (PMID: 10923033). ClinVar contains an entry for this variant (Variation ID: 55390). 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 expected to disrupt BRCA1 protein function. Experimental studies are conflicting or provide insufficient evidence to determine the effect of this variant on BRCA1 function (PMID: 11877378, 19452558, 20516115, 28781887, 30209399, 30765603). 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. |
| Breast Cancer Information Core |
RCV000112494 | SCV000145306 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 1 | no assertion criteria provided | clinical testing | ||
| Research Molecular Genetics Laboratory, |
RCV000496734 | SCV000587459 | uncertain significance | not specified | 2014-01-31 | no assertion criteria provided | research | |
| Brotman Baty Institute, |
RCV000112494 | SCV001237579 | not provided | Breast-ovarian cancer, familial, susceptibility to, 1 | no assertion provided | in vitro |