ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.411dup (p.Leu138fs) (rs886040205)

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Total submissions: 4
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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) RCV000660931 SCV000783169 pathogenic Breast-ovarian cancer, familial 1 2017-12-15 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
Ambry Genetics RCV000509901 SCV000607847 pathogenic Hereditary cancer-predisposing syndrome 2017-12-07 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)
GeneDx RCV000657279 SCV000779010 pathogenic not provided 2017-01-02 criteria provided, single submitter clinical testing This duplication of a single nucleotide in BRCA1 is denoted c.411dupT at the cDNA level and p.Leu138SerfsX4 (L138SfsX4) at the protein level. The normal sequence, with the base that is duplicated in brackets, is GACT[dupT]CTAC. The duplication causes a frameshift which changes a Leucine to a Serine at codon 138, and creates a premature stop codon at position 4 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 RCV000687704 SCV000815289 pathogenic Hereditary breast and ovarian cancer syndrome 2018-04-24 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Leu138Serfs*4) 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: 441309). 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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