Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Evidence- |
RCV000661284 | SCV000783550 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 2017-12-15 | reviewed by expert panel | curation | Variant allele predicted to encode a truncated non-functional protein. |
| Gene |
RCV000235313 | SCV000292746 | pathogenic | not provided | 2015-11-05 | criteria provided, single submitter | clinical testing | This duplication of 2 nucleotides in BRCA1 is denoted c.2693_2694dupAA at the cDNA level and p.Val899LysfsX102 (V899KfsX102) at the protein level. The normal sequence, with the bases that are duplicated in braces, is CCAA[AA]GTCA. Using alternate nomenclature, this variant may be defined as BRCA1 2813insAA, 2812_2813dupAA, or 2813_2814insAA. The duplication causes a frameshift, which changes a Valine to a Lysine at codon 899, and creates a premature stop codon at position 102 of the new reading frame. Although this variant has not, to our knowledge, been reported in the literature, it is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. We consider this variant to be pathogenic. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000589265 | SCV000698974 | likely pathogenic | Hereditary breast ovarian cancer syndrome | 2016-09-15 | criteria provided, single submitter | clinical testing | Variant summary: The BRCA1 c.2693_2694dupAA (p.Val899Lysfs) variant results in a premature termination codon, predicted to cause a truncated or absent BRCA1 protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory (e.g. p.Tyr1703X, p.Val1713fs). Mutation taster predicts a damaging outcome for this variant. This variant is absent in 121354 control chromosomes. The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories; nor evaluated for functional impact by in vivo/vitro studies. One clinical diagnostic laboratory classified this variant as pathogenic. In summary, frameshift nature and absence in controls support pathogenicity of this variant. However, in the absence of clinical information about variant carrier patients and functional studies, the unequivocal pathogenicity of the variant cannot be established, therefore it was classified as likely pathogenic until more information becomes available. |