ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.1265_1266dup (p.Ser423fs)

dbSNP: rs397508850
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Total submissions: 4
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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) RCV000661116 SCV000783364 pathogenic Breast-ovarian cancer, familial, susceptibility to, 1 2017-12-15 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
Labcorp Genetics (formerly Invitae), Labcorp RCV001386708 SCV001587052 pathogenic Hereditary breast ovarian cancer syndrome 2023-05-23 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: 54181). This variant is also known as c.1267insAT (p.S423fs). This premature translational stop signal has been observed in individual(s) with breast cancer (PMID: 22486713). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Ser423Ilefs*8) 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 RCV004018955 SCV005025694 pathogenic Hereditary cancer-predisposing syndrome 2023-12-01 criteria provided, single submitter clinical testing The c.1265_1266dupAT pathogenic mutation, located in coding exon 9 of the BRCA1 gene, results from a duplication of AT at nucleotide position 1265, causing a translational frameshift with a predicted alternate stop codon (p.S423Ifs*8). This alteration was observed in 1/121 early-onset breast cancer patients from Thailand (Ahmad J et al. Clin Genet, 2012 Dec;82:594-8). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). 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.
ClinVar Staff, National Center for Biotechnology Information (NCBI) RCV000577400 SCV000679490 not provided Familial cancer of breast no assertion provided literature only

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