ClinVar Miner

Submissions for variant NM_000527.4(LDLR):c.344G>A (p.Arg115His) (rs201102461)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Cardiovascular Research Group,Instituto Nacional de Saude Doutor Ricardo Jorge RCV000237176 SCV000599327 pathogenic Familial hypercholesterolemia 2016-03-01 criteria provided, single submitter curation
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 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
Color RCV000771221 SCV000903315 uncertain significance Familial hypercholesterolemias 2018-05-23 criteria provided, single submitter clinical testing Variant of Uncertain Significance due to insufficient evidence: This variant (also known as p.Arg94His in the mature protein) is a missense variant located in the third ligand binding domain repeat of the LDLR protein. Computational prediction tools and conservation analyses suggest that this variant may not impact the protein function. Computational splicing tools suggest that this variant may not impact the RNA splicing. Functional assays have shown a moderate effect on LDLR cell surface expression and increased protein localization to the endoplasmic reticulum (PMID: 12837857). However, the clinical significance of these observations is not clear. This variant has been reported in several individuals of Asian ethnicity affected with hypercholesterolemia (PMID: 11005141, 12417285, 15359125, 20538126), but it has also been identified in 48 of 276574 chromosomes (44 of 18844 East Asian chromosomes; 0.23%) in the general population by the Genome Aggregation Database. Segregation of the variant with disease has not been demonstrated. Although this variant has been identified in the general population at a relatively high frequency, available evidence is insufficient to rule out the pathogenicity of this variant conclusively.
Illumina Clinical Services Laboratory,Illumina RCV000237176 SCV000915812 likely pathogenic Familial hypercholesterolemia 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.
LDLR-LOVD, British Heart Foundation RCV000237176 SCV000294641 likely pathogenic Familial hypercholesterolemia 2016-03-25 criteria provided, single submitter literature only
Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde,Academisch Medisch Centrum RCV000237176 SCV000606093 pathogenic Familial hypercholesterolemia no assertion criteria provided research
Soonchunhyang University Bucheon Hospital,Soonchunhyang University Medical Center RCV000237176 SCV000267384 uncertain significance Familial hypercholesterolemia 2016-03-18 criteria provided, single submitter reference population

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