ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.4354A>T (p.Lys1452Ter)

dbSNP: rs398122685
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Total submissions: 6
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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, susceptibility to, 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, susceptibility to, 1 2015-10-02 criteria provided, single submitter clinical testing
Invitae RCV000700553 SCV000829312 pathogenic Hereditary breast ovarian cancer syndrome 2023-04-08 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: 91628). This premature translational stop signal has been observed in individual(s) with a personal and/or family history of breast and/or ovarian cancer (PMID: 29446198). This variant is not present in population databases (gnomAD no frequency). 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. Loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584).
Ambry Genetics RCV002326792 SCV002627927 pathogenic Hereditary cancer-predisposing syndrome 2019-11-26 criteria provided, single submitter clinical testing The p.K1452* pathogenic mutation (also known as c.4354A>T), located in coding exon 11 of the BRCA1 gene, results from an A to T substitution at nucleotide position 4354. This changes the amino acid from a lysine to a stop codon within coding exon 11. This variant has been identified in multiple families diagnosed with breast and/or ovarian cancer (Rebbeck TR et al. Hum. Mutat. 2018 05;39:593-620; Copson ER et al. Lancet Oncol. 2018 02;19:169-180). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
Sharing Clinical Reports Project (SCRP) RCV000077145 SCV000108942 pathogenic Breast-ovarian cancer, familial, susceptibility to, 1 2007-09-04 no assertion criteria provided clinical testing

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