ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.1335_1336del (p.Arg446fs)

dbSNP: rs80357978
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Total submissions: 5
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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, susceptibility to, 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, susceptibility to, 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.
Invitae RCV001386707 SCV001587050 pathogenic Hereditary breast ovarian cancer syndrome 2022-08-16 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 54205). This variant is also known as c.1454delAA. This premature translational stop signal has been observed in individual(s) with family history of breast cancer and/or ovarian cancer (PMID: 14648706, 29446198). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Arg446Serfs*9) in the BRCA1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584).
Breast Cancer Information Core (BIC) (BRCA1) RCV000111591 SCV000144061 pathogenic Breast-ovarian cancer, familial, susceptibility to, 1 1999-12-30 no assertion criteria provided clinical testing

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