Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001308334 | SCV001497780 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2021-11-10 | 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: 55359). This variant has not been reported in the literature in individuals affected with BRCA1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces lysine, which is basic and polar, with threonine, which is neutral and polar, at codon 168 of the BRCA1 protein (p.Lys168Thr). |
| National Health Laboratory Service, |
RCV001308334 | SCV002026029 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2022-04-19 | criteria provided, single submitter | clinical testing | |
| Color Diagnostics, |
RCV003584535 | SCV004361113 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-08-03 | criteria provided, single submitter | clinical testing | This missense variant replaces lysine with threonine at codon 168 of the BRCA1 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). A functional study has reported that this variant does not impact BRCA1 function in a cultured cell homology-directed repair assay (PMID: 30219179). This variant has been reported in individuals with a personal or family history of breast or ovarian cancer (PMID: 24729269, 25556971). 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. |
| Ambry Genetics | RCV003584535 | SCV005025863 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-10-24 | criteria provided, single submitter | clinical testing | The p.K168T variant (also known as c.503A>C), located in coding exon 6 of the BRCA1 gene, results from an A to C substitution at nucleotide position 503. The lysine at codon 168 is replaced by threonine, an amino acid with similar properties. This alteration was identified in an individual diagnosed with breast cancer (Biunno I et al. Fam Cancer, 2014 Sep;13:437-44). This amino acid position is not well conserved in available vertebrate species. 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. |
| Breast Cancer Information Core |
RCV000112721 | SCV000145601 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 1 | 2005-11-29 | no assertion criteria provided | clinical testing |