ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.1321_1322AT[1] (p.Ile441fs) (rs80357570)

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Total submissions: 7
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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) RCV000083169 SCV000299576 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 RCV000083169 SCV000325013 pathogenic Breast-ovarian cancer, familial 1 2015-10-02 criteria provided, single submitter clinical testing
GeneDx RCV000480033 SCV000570485 pathogenic not provided 2016-05-31 criteria provided, single submitter clinical testing This deletion of two nucleotides in BRCA1 is denoted c.1323_1324delAT at the cDNA level and p.Ile441MetfsX2 (I441MfsX2) at the protein level. Using alternate nomenclature, this variant would be defined as BRCA1 1442_1443delAT. The normal sequence, with the bases that are deleted in braces, is TAAT[AT]GTAA. The deletion causes a frameshift which changes an Isoleucine to a Methionine at codon 441, and creates a premature stop codon at position 2 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. Based on currently available evidence, we consider this variant to be pathogenic.
Ambry Genetics RCV001011014 SCV001171291 pathogenic Hereditary cancer-predisposing syndrome 2019-04-26 criteria provided, single submitter clinical testing Alterations resulting in premature truncation (e.g.reading frame shift, nonsense);Rarity in general population databases (dbsnp, esp, 1000 genomes)
Invitae RCV001207888 SCV001379256 pathogenic Hereditary breast and ovarian cancer syndrome 2019-10-21 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Ile441Metfs*2) 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 a BRCA1-related disease. ClinVar contains an entry for this variant (Variation ID: 54201). Loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.
Sharing Clinical Reports Project (SCRP) RCV000083169 SCV000115243 pathogenic Breast-ovarian cancer, familial 1 2009-12-07 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000083169 SCV000144057 pathogenic Breast-ovarian cancer, familial 1 2000-06-12 no assertion criteria provided clinical testing

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