Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002339381 | SCV002642530 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2019-12-12 | criteria provided, single submitter | clinical testing | The p.K1702I variant (also known as c.5105A>T), located in coding exon 16 of the BRCA1 gene, results from an A to T substitution at nucleotide position 5105. The lysine at codon 1702 is replaced by isoleucine, an amino acid with dissimilar properties. One functional study found that this nucleotide substitution is deleterious in a high throughput genome editing haploid cell survival assay (Findlay GM et al. Nature, 2018 10;562:217-222). Based on internal structural analysis, this variant is anticipated to disrupt a region of known function (Ambry internal data; Wu Q et al. Mol Cell. 2016 Feb 4;61(3):434-448). Additionally, this variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD) (Lek M et al. Nature, 2016 08;536:285-91).This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the majority of available evidence to date, this variant is likely to be pathogenic. |
| Labcorp Genetics |
RCV003645189 | SCV004454116 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2023-05-04 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (gnomAD no frequency). This sequence change replaces lysine, which is basic and polar, with isoleucine, which is neutral and non-polar, at codon 1702 of the BRCA1 protein (p.Lys1702Ile). This variant has not been reported in the literature in individuals affected with BRCA1-related conditions. 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 performed at Invitae incorporating data from internal and/or published experimental studies (PMID: 30209399) indicates that this missense variant is expected to disrupt BRCA1 function. ClinVar contains an entry for this variant (Variation ID: 868652). |
| Myriad Genetics, |
RCV001077592 | SCV004931653 | likely pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 2024-03-29 | criteria provided, single submitter | clinical testing | This variant is considered likely pathogenic. Functional studies indicate this variant impacts protein function [PMID: 30209399]. This variant is expected to disrupt protein structure [Myriad internal data]. |
| Brotman Baty Institute, |
RCV001077592 | SCV001243544 | not provided | Breast-ovarian cancer, familial, susceptibility to, 1 | no assertion provided | in vitro |