ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.4354A>T (p.Lys1452Ter) (rs398122685)

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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) RCV000077145 SCV000300107 pathogenic Breast-ovarian cancer, familial 1 2016-09-08 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
GeneDx RCV000159991 SCV000210175 pathogenic not provided 2017-11-28 criteria provided, single submitter clinical testing This variant is denoted BRCA1 c.4354A>T at the cDNA level and p.Lys1452Ter (K1452X) at the protein level. The substitution creates a nonsense variant, which changes a Lysine to a premature stop codon (AAA>TAA), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. This variant, also defined as BRCA1 4473A>T using alternate nomenclature, has not, to our knowledge, been reported in the literature. We consider it to be pathogenic.
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000077145 SCV000325927 pathogenic Breast-ovarian cancer, familial 1 2015-10-02 criteria provided, single submitter clinical testing
Invitae RCV000700553 SCV000829312 pathogenic Hereditary breast and ovarian cancer syndrome 2018-04-16 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Lys1452*) 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 been reported in a family with increased risk of breast and ovarian cancers (PMID: 29446198). ClinVar contains an entry for this variant (Variation ID: 91628). 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) RCV000077145 SCV000108942 pathogenic Breast-ovarian cancer, familial 1 2007-09-04 no assertion criteria provided clinical testing

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