ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.670+1G>T (rs398122706)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000203857 SCV000260418 uncertain significance Hereditary breast and ovarian cancer syndrome 2019-07-12 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 9 of the BRCA1 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been reported in individuals in the Leiden Open-source Variation Database (PMID: 21520333). ClinVar contains an entry for this variant (Variation ID: 91661). Experimental studies have shown that a different variant that gives rise to a nearly identical effect (c.670+1delG) results in the generation of an aberrant transcript that leads to the out-of-frame activation of a cryptic donor splice site in exon 9, located 1 nucleotide upstream of the natural splice site (PMID: 24667779). However, an in-frame BRCA1 isoform that skips exons 8 and 9 (also known as exons 9 and 10) is naturally expressed in normal blood and breast tissue, suggesting that this splice donor variant may not be deleterious (PMID: 24569164). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics RCV000213883 SCV000278115 uncertain significance Hereditary cancer-predisposing syndrome 2018-10-08 criteria provided, single submitter clinical testing Insufficient evidence
Sharing Clinical Reports Project (SCRP) RCV000077178 SCV000108975 pathogenic Breast-ovarian cancer, familial 1 2009-12-21 no assertion criteria provided clinical testing

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