ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.1918C>T (p.Gln640Ter)

dbSNP: rs886039981
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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) RCV000256851 SCV000323372 pathogenic Breast-ovarian cancer, familial, susceptibility to, 1 2016-10-18 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000256851 SCV000325181 pathogenic Breast-ovarian cancer, familial, susceptibility to, 1 2015-10-02 criteria provided, single submitter clinical testing
Invitae RCV000811225 SCV000951481 pathogenic Hereditary breast ovarian cancer syndrome 2023-07-11 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln640*) 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). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with breast and/or ovarian cancer and breast cancer (PMID: 24633894, 28477318). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 266201). For these reasons, this variant has been classified as Pathogenic.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV003477872 SCV004222579 pathogenic not provided 2022-11-01 criteria provided, single submitter clinical testing This nonsense variant causes the premature termination of BRCA1 protein synthesis. It has not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org). In the published literature, the variant has been reported in individuals with breast cancer (PMID: 24633894 (2014)). The variant has also been reported in a worldwide screening study of BRCA1 mutation positive families (PMID: 29446198 (2018)). Based on the available information, this variant is classified as pathogenic.

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