ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.1335_1336del (p.Arg446fs) (rs80357978)

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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) RCV000111591 SCV000299580 pathogenic Breast-ovarian cancer, familial 1 2016-09-08 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000111591 SCV000325021 pathogenic Breast-ovarian cancer, familial 1 2015-10-02 criteria provided, single submitter clinical testing
GeneDx RCV000657214 SCV000778940 pathogenic not provided 2017-09-21 criteria provided, single submitter clinical testing This deletion of two nucleotides in BRCA1 is denoted c.1335_1336delAA at the cDNA level and p.Arg446SerfsX9 (R446SfsX9) at the protein level. The normal sequence, with the bases that are deleted in brackets, is GTGA[delAA]GAGT. The deletion causes a frameshift which changes an Arginine to a Serine at codon 446, and creates a premature stop codon at position 9 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. Also described as BRCA1 1454delAA using alternate nomenclature, this variant has been observed in at least one individual with family history of breast or ovarian cancer (Kadouri 2004). We consider BRCA1 c.1335_1336delAA to be pathogenic.
Breast Cancer Information Core (BIC) (BRCA1) RCV000111591 SCV000144061 pathogenic Breast-ovarian cancer, familial 1 1999-12-30 no assertion criteria provided clinical testing

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