ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.3964A>T (p.Lys1322Ter) (rs80357343)

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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) RCV000112218 SCV000300047 pathogenic Breast-ovarian cancer, familial 1 2016-09-08 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
Ambry Genetics RCV000563165 SCV000660947 pathogenic Hereditary cancer-predisposing syndrome 2016-10-21 criteria provided, single submitter clinical testing The p.K1322* pathogenic mutation (also known as c.3964A>T), located in coding exon 9 of the BRCA1 gene, results from an A to T substitution at nucleotide position 3964. This changes the amino acid from a lysine to a stop codon within coding exon 9. 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000590774 SCV000699089 likely pathogenic Hereditary breast and ovarian cancer syndrome 2017-02-13 criteria provided, single submitter clinical testing Variant summary: The BRCA1 c.3964A>T (p.Lys1322X) variant results in a premature termination codon, predicted to cause a truncated or absent BRCA1 protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory (e.g. c.3972_3974delinsAA, c.4035delA, c.4041_4042delAG, c.4065_4068delTCAA, c.4096+3A>G). Mutation Taster predicts a damaging outcome for this variant. This variant is absent in 121396 control chromosomes. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic. The variant of interest has not, to our knowledge, been reported in affected individuals via publications nor evaluated for functional impact by in vivo/vitro studies. Taken together, this variant is classified as likely pathogenic.
Invitae RCV000590774 SCV001592839 pathogenic Hereditary breast and ovarian cancer syndrome 2018-05-16 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Lys1322*) 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 individuals in the Leiden Open-source Variation Database (PMID: 21520333) and Breast Cancer Information Core database (PMID: 10923033). ClinVar contains an entry for this variant (Variation ID: 55059). Loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.
Breast Cancer Information Core (BIC) (BRCA1) RCV000112218 SCV000144926 pathogenic Breast-ovarian cancer, familial 1 2002-05-29 no assertion criteria provided clinical testing

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