ClinVar Miner

Submissions for variant NM_000527.4(LDLR):c.1358+2T>C (rs193922567)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Robarts Research Institute,Western University RCV000408853 SCV000484785 likely pathogenic Familial hypercholesterolemia 1 criteria provided, single submitter clinical testing
Invitae RCV001234476 SCV001407126 pathogenic Familial hypercholesterolemia 2019-10-22 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 9 of the LDLR 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). Disruption of this splice site has been observed in several individuals affected with hypercholesterolemia (PMID: 11196104, 30293936, Invitae). ClinVar contains an entry for this variant (Variation ID: 369862). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in LDLR are known to be pathogenic (PMID: 20809525, 28645073). For these reasons, this variant has been classified as Pathogenic.
Brunham Lab, Centre for Heart and Lung Innovation,University of British Columbia RCV000408853 SCV001432629 pathogenic Familial hypercholesterolemia 1 2019-06-05 criteria provided, single submitter research

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