ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.1292del (p.Leu431fs)

dbSNP: rs80357528
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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) RCV000077060 SCV000299571 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000590574 SCV000698843 likely pathogenic Hereditary breast ovarian cancer syndrome 2017-07-24 criteria provided, single submitter clinical testing Variant summary: The BRCA1 c.1292delT (p.Leu431Tyrfs) 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. p.Glu1470X, p.Glu1535X, p.Tyr1703X, etc.). This variant has been reported in multiple individuals undergoing clinical testing of BRCA1/2 by clinical laboratories and during validation of assay methods (van der Stoep_2009, Mattocks_2010). This variant is absent in 121238 control chromosomes from ExAC. In addition, multiple clinical diagnostic laboratories/reputable databases have classified this variant as pathogenic. Taken together, this variant is classified as likely pathogenic.
Invitae RCV000590574 SCV000831016 pathogenic Hereditary breast ovarian cancer syndrome 2022-06-03 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: 91543). This variant has not been reported in the literature in individuals affected with BRCA1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Leu431Tyrfs*10) 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 RCV002381391 SCV002692836 pathogenic Hereditary cancer-predisposing syndrome 2021-09-03 criteria provided, single submitter clinical testing The c.1292delT pathogenic mutation, located in coding exon 9 of the BRCA1 gene, results from a deletion of one nucleotide at nucleotide position 1292, causing a translational frameshift with a predicted alternate stop codon (p.L431Yfs*10). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). 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) RCV000077060 SCV000108857 pathogenic Breast-ovarian cancer, familial, susceptibility to, 1 2008-01-24 no assertion criteria provided clinical testing

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