ClinVar Miner

Submissions for variant NM_000527.5(LDLR):c.2311+1G>T

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
LDLR-LOVD, British Heart Foundation RCV000237602 SCV000295942 likely pathogenic Hypercholesterolemia, familial, 1 2016-03-25 criteria provided, single submitter literature only
Centre de Génétique Moléculaire et Chromosomique, Unité de génétique de l'Obésité et des Dyslipidémies, APHP, GH Hôpitaux Universitaires Pitié-Salpêtrière / Charles-Foix RCV000237602 SCV000503479 pathogenic Hypercholesterolemia, familial, 1 2016-12-16 criteria provided, single submitter clinical testing subjects mutated among 2600 FH index cases screened = 2 , family member = 1 / FH Italia, 12% LDLR activity
U4M - Lille University & CHRU Lille, Université de Lille - CHRU de Lille RCV000237602 SCV000583941 pathogenic Hypercholesterolemia, familial, 1 2017-03-30 criteria provided, single submitter clinical testing
Laboratory of Genetics and Molecular Cardiology, University of São Paulo RCV000237602 SCV000588647 pathogenic Hypercholesterolemia, familial, 1 2016-03-01 criteria provided, single submitter research
Invitae RCV001385153 SCV001584913 pathogenic Familial hypercholesterolemia 2020-05-06 criteria provided, single submitter clinical testing Disruption of this splice site has been observed in individual(s) with familial hypercholesterolemia (PMID: 7545204, 16389549, 20809525). ClinVar contains an entry for this variant (Variation ID: 252274). This variant is not present in population databases (ExAC no frequency). This sequence change affects a donor splice site in intron 15 of the LDLR gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. 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. For these reasons, this variant has been classified as Pathogenic. 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).
Revvity Omics, Revvity RCV000237602 SCV002017128 pathogenic Hypercholesterolemia, familial, 1 2020-03-23 criteria provided, single submitter clinical testing
Ambry Genetics RCV002446479 SCV002735337 pathogenic Cardiovascular phenotype 2017-11-27 criteria provided, single submitter clinical testing The c.2311+1G>T intronic pathogenic mutation results from a G to T substitution one nucleotide after coding exon 15 of the LDLR gene. This mutation was reported in two apparently unrelated individuals with familial hypercholesterolemia, and was described to segregate with the disease in their families (Marduel M et al. Hum. Mutat., 2010 Nov;31:E1811-24). In addition to the clinical data presented in the literature, alterations that disrupt the canonical splice site are expected to cause aberrant splicing, resulting in an abnormal protein or a transcript that is subject to nonsense-mediated mRNA decay. As such, this alteration is classified as a disease-causing mutation.
Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde, Academisch Medisch Centrum RCV000237602 SCV000606630 pathogenic Hypercholesterolemia, familial, 1 no assertion criteria provided research

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