Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000539904 | SCV000635839 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2017-02-16 | criteria provided, single submitter | clinical testing | Experimental studies and prediction algorithms are not available for this variant, and the functional significance of the substituted amino acids is currently unknown. In summary, this is a novel in-frame deletion and insertion with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a BRCA1-related disease. This variant, c.2235_2236delinsCT,  is a complex sequence change that results in the deletion of glutamic acid and aspartic acid residues and the insertion of aspartic acid and tyrosine residues in the BRCA1 protein (p.Glu745_Asp746delinsAspTyr). |
Ambry Genetics | RCV002431582 | SCV002727901 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-09-09 | criteria provided, single submitter | clinical testing | The c.2235_2236delAGinsCT variant (also known as p.E745_D746delinsDY), located in coding exon 9 of the BRCA1 gene, results from an in-frame deletion of AG and insertion of CT at nucleotide positions 2235 to 2236. This results in the substitution of the glutamic acid and aspartic acid residues for aspartic acid any tyrosine residues at codons 745 and 746. These amino acid positions are not well conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis (Choi Y et al. PLoS ONE. 2012; 7(10):e46688). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
University of Washington Department of Laboratory Medicine, |
RCV002431582 | SCV003848027 | 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). |