ClinVar Miner

Submissions for variant NM_000527.5(LDLR):c.1358+1G>A

dbSNP: rs775924858
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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 RCV000237640 SCV000295382 likely pathogenic Hypercholesterolemia, familial, 1 2016-03-25 criteria provided, single submitter literature only
Robarts Research Institute, Western University RCV000237640 SCV000484786 likely pathogenic Hypercholesterolemia, familial, 1 criteria provided, single submitter clinical testing
Centre de Génétique Moléculaire et Chromosomique, Unité de génétique de l'Obésité et des Dyslipidémies, APHP, GH Hôpitaux Universitaires Pitié-Salpêtrière / Charles-Foix RCV000237640 SCV000503339 pathogenic Hypercholesterolemia, familial, 1 2016-12-16 criteria provided, single submitter clinical testing subject mutated among 2600 FH index cases screened = 1
U4M - Lille University & CHRU Lille, Université de Lille - CHRU de Lille RCV000237640 SCV000583824 pathogenic Hypercholesterolemia, familial, 1 2017-03-30 criteria provided, single submitter clinical testing
Fundacion Hipercolesterolemia Familiar RCV000237640 SCV000607590 pathogenic Hypercholesterolemia, familial, 1 2016-03-01 criteria provided, single submitter research
Quest Diagnostics Nichols Institute San Juan Capistrano RCV002479949 SCV002774353 pathogenic not provided 2021-08-02 criteria provided, single submitter clinical testing This variant is located in a canonical splice-donor site and interferes with normal LDLR mRNA splicing. The variant has been reported in individuals affected with Familial Hypercholesteremia (FH) in the published literature (PMID: 24632281 (2014), 22390909 (2012), 19208450 (2009), 16627557 (2006), 15701167 (2005), 15241806 (2004)). Therefore, the variant is classified as pathogenic.
Invitae RCV003581623 SCV004298356 pathogenic Familial hypercholesterolemia 2023-05-19 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 251802). This variant is also known as IVS9+1G>A. Disruption of this splice site has been observed in individuals with familial hypercholesterolemia (PMID: 8314561, 15701167, 18096825). This variant is present in population databases (rs775924858, gnomAD 0.0009%). This sequence change affects a donor splice site in intron 9 of the LDLR gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site 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).
Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde, Academisch Medisch Centrum RCV000237640 SCV000606404 pathogenic Hypercholesterolemia, familial, 1 no assertion criteria provided research

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