ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.4088C>A (p.Ser1363Ter)

dbSNP: rs398122680
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Total submissions: 3
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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) RCV000660912 SCV000783148 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.
Ambry Genetics RCV000510005 SCV000607965 pathogenic Hereditary cancer-predisposing syndrome 2021-11-03 criteria provided, single submitter clinical testing The p.S1363* variant (also known as c.4088C>A), located in coding exon 9 of the BRCA1 gene, results from a C to A substitution at nucleotide position 4088. This changes the amino acid from a serine to a stop codon within coding exon 9. This alteration was previously reported in a breast cancer patient in one study that was aimed at developing novel diagnostic applications (Michils G et al J Mol Diagn. 2012 Nov;14(6):623-30). 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.
Invitae RCV001234780 SCV001407439 pathogenic Hereditary breast ovarian cancer syndrome 2022-01-11 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: 441374). 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.Ser1363*) 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).

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