ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.2275C>T (p.Gln759Ter)

dbSNP: rs80356999
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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) RCV000111814 SCV000299736 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.
Invitae RCV001380382 SCV001578429 pathogenic Hereditary breast ovarian cancer syndrome 2023-04-23 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: 54519). This variant is also known as 2394C>T. This premature translational stop signal has been observed in individual(s) with hereditary breast and/or ovarian cancer and early onset breast cancer (PMID: 22752604, 26848529). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change creates a premature translational stop signal (p.Gln759*) 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 RCV002444510 SCV002732124 pathogenic Hereditary cancer-predisposing syndrome 2020-11-04 criteria provided, single submitter clinical testing The p.Q759* pathogenic mutation (also known as c.2275C>T), located in coding exon 9 of the BRCA1 gene, results from a C to T substitution at nucleotide position 2275. This changes the amino acid from a glutamine to a stop codon within coding exon 9. This alteration has been reported in individuals of Asian descent with breast cancer (Juwle A et al. Med Oncol, 2012 Dec;29:3272-81; Bhaskaran SP et al. Int J Cancer, 2019 08;145:962-973. 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.
Breast Cancer Information Core (BIC) (BRCA1) RCV000111814 SCV000144364 pathogenic Breast-ovarian cancer, familial, susceptibility to, 1 2004-02-20 no assertion criteria provided clinical testing

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