ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.4508C>G (p.Ser1503Ter) (rs80357437)

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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) RCV000661371 SCV000783644 pathogenic Breast-ovarian cancer, familial 1 2017-12-15 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000508623 SCV000605880 pathogenic not provided 2016-09-15 criteria provided, single submitter clinical testing
Invitae RCV000698399 SCV000827060 pathogenic Hereditary breast and ovarian cancer syndrome 2018-05-18 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Ser1503*) in the BRCA1 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with BRCA1-related disease. ClinVar contains an entry for this variant (Variation ID: 440476). A different variant (c.4508C>A, also known as 4627C>A) giving rise to the same protein effect observed here (p.Ser1503*) has been reported in several individuals and families affected with breast and/or ovarian cancer (PMID: 12181777, 16683254, 27553291, 16998791, 28724667), indicating that this residue may be critical for protein function. Loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.

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