ClinVar Miner

Submissions for variant NM_000527.5(LDLR):c.2312-3C>A

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
LDLR-LOVD, British Heart Foundation RCV000211656 SCV000295947 likely pathogenic Familial hypercholesterolemia 1 2016-03-25 criteria provided, single submitter literature only
Laboratory of Genetics and Molecular Cardiology, University of São Paulo RCV000211656 SCV000588653 likely pathogenic Familial hypercholesterolemia 1 2016-03-01 criteria provided, single submitter research
Integrated Genetics/Laboratory Corporation of America RCV000586092 SCV000697226 pathogenic Familial hypercholesterolemia 2016-09-06 criteria provided, single submitter clinical testing Variant summary: The LDLR c.2312-3C>A variant involves the alteration of a non-conserved intronic nucleotide. One in silico tool predicts a damaging outcome for this variant, and 5/5 splicing algorithms predict this variant to reduce the splice acceptor site strength. LDLR residual activity on stimulated T-lymphocytes from multiple heterozygous patients were approximately 50% of normal activity, suggesting that this variant results in little to no residual activity. This variant was not found in large and broad populations from ExAC. It has been reported as one of the common pathogenic variants that causes FH. Furthermore, multiple clinical diagnostic laboratories/reputable databases classified this variant as likely pathogenic/pathogenic. Taken together, this variant is classified as pathogenic.
Department of Human Genetics,Laborarztpraxis Dres. Walther, Weindel und Kollegen RCV000211656 SCV000987039 pathogenic Familial hypercholesterolemia 1 2018-10-22 criteria provided, single submitter clinical testing The mutation leads to a change in the splice acceptor in intron 15 of the LDLR gene. It has already been described in the literature, detected in patients with familial hypercholesterolemia, and associated with elevated cholesterol and LDL-C levels. In in vitro models, the mutation leads to almost complete loss of LDL receptor activity. We observed this mutation in a patient with TC up to 520 mg/dl and LDL-C approx 420 mg/dl at the age of 45 years. PMID: 11317362, 21865347
Brunham Lab, Centre for Heart and Lung Innovation,University of British Columbia RCV000211656 SCV001432564 uncertain significance Familial hypercholesterolemia 1 2019-06-17 criteria provided, single submitter research
Cardiovascular Genetics Laboratory,PathWest Laboratory Medicine WA - Fiona Stanley Hospital RCV000211656 SCV000268664 pathogenic Familial hypercholesterolemia 1 2009-07-24 no assertion criteria provided clinical testing
Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde,Academisch Medisch Centrum RCV000211656 SCV000606631 pathogenic Familial hypercholesterolemia 1 no assertion criteria provided research

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