ClinVar Miner

Submissions for variant NM_000527.4(LDLR):c.1291G>A (p.Ala431Thr) (rs28942079)

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Total submissions: 15
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Blueprint Genetics RCV000003883 SCV000264001 likely pathogenic Familial hypercholesterolemia 1 2015-09-17 criteria provided, single submitter clinical testing
LDLR-LOVD, British Heart Foundation RCV000003883 SCV000295346 likely pathogenic Familial hypercholesterolemia 1 2016-03-25 criteria provided, single submitter literature only
Cardiovascular Research Group,Instituto Nacional de Saude Doutor Ricardo Jorge RCV000003883 SCV000322941 pathogenic Familial hypercholesterolemia 1 2016-03-01 criteria provided, single submitter research 0/190 non-FH alleles; 0/100 Chinese normolipidemic individuals; 0/100 healthy control individuals
Robarts Research Institute,Western University RCV000003883 SCV000484702 likely pathogenic Familial hypercholesterolemia 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 RCV000003883 SCV000503329 likely pathogenic Familial hypercholesterolemia 1 2016-12-16 criteria provided, single submitter clinical testing subjects mutated among 2600 FH index cases screened = 4 , family members = 11 with co-segregation / FH-Algeria-2, 5 to 15% LDLR activity / Software predictions: Damaging
Molecular Genetics Laboratory,Centre for Cardiovascular Surgery and Transplantation RCV000003883 SCV000540810 likely pathogenic Familial hypercholesterolemia 1 2016-11-05 criteria provided, single submitter clinical testing
U4M - Lille University & CHRU Lille, Université de Lille - CHRU de Lille RCV000003883 SCV000583817 pathogenic Familial hypercholesterolemia 1 2017-03-30 criteria provided, single submitter clinical testing
Laboratory of Genetics and Molecular Cardiology, University of São Paulo RCV000003883 SCV000588572 pathogenic Familial hypercholesterolemia 1 2016-03-01 criteria provided, single submitter research
Fundacion Hipercolesterolemia Familiar RCV000003883 SCV000607581 pathogenic Familial hypercholesterolemia 1 2016-03-01 criteria provided, single submitter research
Iberoamerican FH Network RCV000003883 SCV000748145 pathogenic Familial hypercholesterolemia 1 2016-03-01 criteria provided, single submitter research
Invitae RCV000806811 SCV000946830 pathogenic Familial hypercholesterolemia 2018-09-11 criteria provided, single submitter clinical testing This sequence change replaces alanine with threonine at codon 431 of the LDLR protein (p.Ala431Thr). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and threonine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in several individuals affected with familial hypercholesterolemia (FH), including individuals with homozygous FH (HoFH) (PMID: 12837857, 21382890, 25461735, 17765246, 10447263, 27824480, 17347910, 23815734, 15200491, 28104544). This variant is also described as Ala410Thr (A410T) in the literature. ClinVar contains an entry for this variant (Variation ID: 3695). Experimental studies have shown that this missense change leads to a reduction in LDL receptor amount and activity (PMID: 12837857). For these reasons, this variant has been classified as Pathogenic.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000985760 SCV001134248 likely pathogenic not provided 2019-05-28 criteria provided, single submitter clinical testing The best available variant frequency is uninformative. Found in at least one symptomatic patient. Predicted to have a damaging effect on the protein. Assessment of experimental evidence suggests this variant results in abnormal protein function.
OMIM RCV000003883 SCV000024048 pathogenic Familial hypercholesterolemia 1 2014-08-27 no assertion criteria provided literature only
Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde,Academisch Medisch Centrum RCV000003883 SCV000606382 pathogenic Familial hypercholesterolemia 1 no assertion criteria provided research
Diagnostic Laboratory, Department of Genetics,University Medical Center Groningen RCV000003883 SCV000733819 pathogenic Familial hypercholesterolemia 1 no assertion criteria provided clinical testing

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