ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.744del (p.Thr249fs) (rs1060502360)

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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) RCV000661258 SCV000783522 pathogenic Breast-ovarian cancer, familial 1 2017-12-15 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
Invitae RCV000458382 SCV000549403 pathogenic Hereditary breast and ovarian cancer syndrome 2016-08-10 criteria provided, single submitter clinical testing This sequence change deletes 1 nucleotide in exon 10 of the BRCA1 mRNA (c.744delC), causing a frameshift at codon 249. This creates a premature translational stop signal (p.Thr249Leufs*49) and is expected to result in an absent or disrupted protein product. Loss-of-function variants in BRCA1 are known to be pathogenic. This particular variant has been reported in the literature in an individual with breast cancer, who also had a family history of breast and ovarian cancer (PMID: 22160602). For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV000657217 SCV000778943 pathogenic not provided 2018-02-23 criteria provided, single submitter clinical testing This deletion of one nucleotide in BRCA1 is denoted c.744delC at the cDNA level and p.Thr249LeufsX49 (T249LfsX49) at the protein level. Using alternate nomenclature, this variant would be defined as BRCA1 863delC or 862delC. The normal sequence, with the base that is deleted in brackets, is ACAC[delC]ACTG. The deletion causes a frameshift which changes a Threonine to a Leucine at codon 249, and creates a premature stop codon at position 49 of the new reading frame. This variant is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. BRCA1 c.744delC has been observed in association with Hereditary Breast and Ovarian Cancer syndrome (Schneegans 2012). We consider this variant to be pathogenic.

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