ClinVar Miner

Submissions for variant NM_000527.5(LDLR):c.344G>A (p.Arg115His) (rs201102461)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Soonchunhyang University Bucheon Hospital,Soonchunhyang University Medical Center RCV000237176 SCV000267384 uncertain significance Familial hypercholesterolemia 1 2016-03-18 criteria provided, single submitter reference population
LDLR-LOVD, British Heart Foundation RCV000237176 SCV000294641 likely pathogenic Familial hypercholesterolemia 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 RCV000237176 SCV000503144 likely benign Familial hypercholesterolemia 1 2016-12-16 criteria provided, single submitter clinical testing subject mutated among 2600 FH index cases screened = 1 /previously described in association with FH / Software predictions: Conflicting
Cardiovascular Research Group,Instituto Nacional de Saude Doutor Ricardo Jorge RCV000237176 SCV000599327 pathogenic Familial hypercholesterolemia 1 2016-03-01 criteria provided, single submitter curation
Color RCV000771221 SCV000903315 uncertain significance Familial hypercholesterolemia 2019-12-19 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000237176 SCV000915812 likely pathogenic Familial hypercholesterolemia 1 2017-05-01 criteria provided, single submitter clinical testing The LDLR c.344G>A (p.Arg115His) missense variant has been reported in five studies and is found in a total of eight individuals with hypercholesterolemia, including one individual who carried the variant in a compound heterozygous state with a stop-gained variant and seven individuals who carried the variant in a heterozygous state (Khoo et al. 2000; Yu et al. 2002; Kim et al. 2004; Chiou et al. 2011; Mabuchi et al. 2011). Control data are unavailable for this variant, which is reported at a frequency of 0.00234 in the East Asian population of the Genome Aggregation Database. Based on the evidence, the p.Arg115His variant is classified as likely pathogenic for familial hypercholesterolemia. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Invitae RCV000771221 SCV001225051 uncertain significance Familial hypercholesterolemia 2019-11-01 criteria provided, single submitter clinical testing This sequence change replaces arginine with histidine at codon 115 of the LDLR protein (p.Arg115His). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and histidine. This variant is present in population databases (rs201102461, ExAC 0.2%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This variant has been observed in individuals affected with familial hypercholesterolemia (PMID: 9399845, 15359125, 29399563, 28502495, 18718593, 28932795, 11005141, 12417285). This variant is also known as R94H in the literature. ClinVar contains an entry for this variant (Variation ID: 225402). This variant has been reported to have conflicting or insufficient data to determine the effect on LDLR protein function (PMID: 12837857, 27821657). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde,Academisch Medisch Centrum RCV000237176 SCV000606093 pathogenic Familial hypercholesterolemia 1 no assertion criteria provided research

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