ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.4787C>A (p.Ser1596Ter)

dbSNP: rs80357429
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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) RCV000661272 SCV000783537 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.
GeneDx RCV000486809 SCV000568386 pathogenic not provided 2020-05-12 criteria provided, single submitter clinical testing Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed in large population cohorts (Lek 2016); Truncating variants in this gene are considered pathogenic by a well-established clinical consortium and/or database; Also known as 4906C>A; This variant is associated with the following publications: (PMID: 30322717, 25556971, 30199306)
Ambry Genetics RCV000509938 SCV000607856 pathogenic Hereditary cancer-predisposing syndrome 2022-05-06 criteria provided, single submitter clinical testing The p.S1596* pathogenic mutation (also known as c.4787C>A), located in coding exon 14 of the BRCA1 gene, results from a C to A substitution at nucleotide position 4787. This changes the amino acid from a serine to a stop codon within coding exon 14. 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.
Invitae RCV001045842 SCV001209716 pathogenic Hereditary breast ovarian cancer syndrome 2022-12-29 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: 420037). This premature translational stop signal has been observed in individual(s) with breast and/or ovarian cancer (PMID: 25556971). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Ser1596*) 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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