Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Color Diagnostics, |
RCV000777511 | SCV000913373 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-07-05 | criteria provided, single submitter | clinical testing | This missense variant replaces cysteine with tryptophan at codon 1251 of the BRCA1 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |
Labcorp Genetics |
RCV001869125 | SCV002269338 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2020-11-17 | 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. This variant has not been reported in the literature in individuals with BRCA1-related conditions. ClinVar contains an entry for this variant (Variation ID: 631326). This variant is not present in population databases (ExAC no frequency). This sequence change replaces cysteine with tryptophan at codon 1251 of the BRCA1 protein (p.Cys1251Trp). The cysteine residue is weakly conserved and there is a large physicochemical difference between cysteine and tryptophan. |
University of Washington Department of Laboratory Medicine, |
RCV000777511 | SCV003848173 | 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). |
Ambry Genetics | RCV000777511 | SCV004004303 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-03-17 | criteria provided, single submitter | clinical testing | The p.C1251W variant (also known as c.3753T>G), located in coding exon 9 of the BRCA1 gene, results from a T to G substitution at nucleotide position 3753. The cysteine at codon 1251 is replaced by tryptophan, an amino acid with highly dissimilar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |