ClinVar Miner

Submissions for variant NM_000527.4(LDLR):c.2441G>A (p.Arg814Gln) (rs5928)

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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CSER_CC_NCGL; University of Washington Medical Center RCV000148584 SCV000190298 uncertain significance Hypercholesterolaemia 2014-06-01 no assertion criteria provided research
Centre de Génétique Moléculaire et Chromosomique, Unité de génétique de l'Obésité et des Dyslipidémies,APHP, GH Hôpitaux Universitaires Pitié-Salpêtrière / Charles-Foix RCV000237126 SCV000503489 likely benign Familial hypercholesterolemia 2016-12-16 criteria provided, single submitter clinical testing subjects mutated among 2600 FH index cases screened = 3 , family member = 1/previously described in association with FH/Software predictions: Conflicting
Color RCV000776249 SCV000911501 likely benign Familial hypercholesterolemias 2017-12-12 criteria provided, single submitter clinical testing
Dept. of Genetics and Pharmacogenomics, Merck Research Labs RCV000162024 SCV000189627 not provided not provided no assertion provided in vitro
Integrated Genetics/Laboratory Corporation of America RCV000162024 SCV000697230 uncertain significance not provided 2017-01-16 criteria provided, single submitter clinical testing Variant summary: The LDLR c.2441G>A (p.Arg814Gln) variant involves the alteration of a conserved nucleotide. 2/4 in silico tools predict a benign outcome for this variant (SNPs&GO not captured due to low reliability index). This variant was found in 34/121530 control chromosomes, predominantly observed in the African subpopulation at a frequency of 0.0031712 (33/10406). This frequency is about 3 times the estimated maximal expected allele frequency of a pathogenic LDLR variant (0.0010005), suggesting this is possibly a benign polymorphism found primarily in the populations of African origin. This variant has been reported in multiple affected individuals (mostly with African ethnicities) without strong evidence for causality. In addition, one clinical diagnostic laboratory/database classified this variant as likely benign and another one classified it as VUS, all without evidence for independent evaluation. In vivo study of LDL metabolism showed this variant with a reduced in vivo activity of LDL-R (80% of WT; Arca_1997 and Arca_1994). Taken together, this variant is classified as VUS.
Invitae RCV000237126 SCV000752439 likely benign Familial hypercholesterolemia 2017-11-17 criteria provided, single submitter clinical testing
LDLR-LOVD, British Heart Foundation RCV000237126 SCV000296010 likely benign Familial hypercholesterolemia 2016-03-25 criteria provided, single submitter literature only
Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde,Academisch Medisch Centrum RCV000237126 SCV000606653 pathogenic Familial hypercholesterolemia no assertion criteria provided research
Laboratory of Genetics and Molecular Cardiology,University of São Paulo RCV000237126 SCV000588667 uncertain significance Familial hypercholesterolemia 2016-03-01 criteria provided, single submitter research
U4M - Lille University & CHRU Lille, Université de Lille - CHRU de Lille RCV000237126 SCV000583953 likely pathogenic Familial hypercholesterolemia 2017-03-30 criteria provided, single submitter clinical testing

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