ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.5427dup (p.Val1810fs) (rs1555574739)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000661209 SCV000783469 pathogenic Breast-ovarian cancer, familial 1 2017-12-15 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000504023 SCV000591631 likely pathogenic Hereditary breast and ovarian cancer syndrome 2014-06-27 criteria provided, single submitter clinical testing
Invitae RCV000504023 SCV000758804 pathogenic Hereditary breast and ovarian cancer syndrome 2017-11-15 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the BRCA1 gene (p.Val1810Cysfs*20). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 54 amino acids of the BRCA1 protein. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with BRCA1-related disease. ClinVar contains an entry for this variant (Variation ID: 433737). This variant is expected to disrupt a portion of the C-terminal region of the BRCA1 protein containing the BRCT domain (residues Val1646-Pro1859) (PMID: 25652403). Although functional studies have not been performed for this particular variant, the BRCT domain is critical for BRCA1 DNA repair activity (PMID: 11573086, 14576433, 15133503, 25652403). This suggests that disruption of this region of the BRCA1 protein is causative of disease. For these reasons, this variant has been classified as Pathogenic.

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