ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.374dup (p.Gln126fs) (rs1555596392)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000657508 SCV000779244 pathogenic not provided 2018-04-17 criteria provided, single submitter clinical testing This duplication of one nucleotide in BRCA1 is denoted c.374dupT at the cDNA level and p.Gln126ProfsX16 (Q126PfsX16) at the protein level. The normal sequence, with the base that is duplicated in brackets, is ATCA[dupT]CCAA. The duplication causes a frameshift which changes a Glutamine to a Proline at codon 126, and creates a premature stop codon at position 16 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.
Invitae RCV000805958 SCV000945934 pathogenic Hereditary breast and ovarian cancer syndrome 2018-10-15 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln126Profs*16) in the BRCA1 gene. It is expected to result in an absent or disrupted protein product. 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: 545900). Loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.

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