ClinVar Miner

Submissions for variant NM_000527.4(LDLR):c.970G>A (p.Gly324Ser) (rs72658860)

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Total submissions: 12
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CSER_CC_NCGL; University of Washington Medical Center RCV000148566 SCV000190279 likely benign 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 RCV000237236 SCV000503271 benign Familial hypercholesterolemia 2016-12-16 criteria provided, single submitter clinical testing subjects mutated among 2600 FH index cases screened = 2 / Software predictions: Damaging
Color RCV000771170 SCV000903099 benign Familial hypercholesterolemias 2017-08-29 criteria provided, single submitter clinical testing
Dept. of Genetics and Pharmacogenomics, Merck Research Labs RCV000162021 SCV000189624 not provided not provided no assertion provided in vitro
Iberoamerican FH Network RCV000237236 SCV000748045 uncertain significance Familial hypercholesterolemia 2016-03-01 criteria provided, single submitter research
Integrated Genetics/Laboratory Corporation of America RCV000162021 SCV000697255 likely benign not provided 2016-07-25 criteria provided, single submitter clinical testing Variant summary: The LDLR c.970G>A (p.Gly324Ser) variant involves the alteration of a conserved nucleotide and results in a replacement of a small size and hydrophobic Glycine (G) with a small size and polar Serine (S) located ) within the first of the three cystein-rich repeats of the epidermal growth factor homology domain that also contributes to ligand binding. 4/4 in silico tools predict a damaging outcome for this variant (SNPs&GO not captured due to low reliability index). This variant was found in 140/120542 control chromosomes, predominantly observed in the African subpopulation at a frequency of 0.0131784 (135/10244). This frequency is about 13 times the estimated maximal expected allele frequency of a pathogenic LDLR variant (0.0010005), suggesting this is likely a benign polymorphism found primarily in the populations of African origin. The variant was reported in several Familial Hypercholesterolemia patients, however without strong evidence for pathogenicity. Moreover, in one FH family, the variant was found to co-occur with pathogenic/likely pathogenic variant and not co-segregate with the disease, indicating neutrality of this variant. In addition, a clinical diagnostic laboratory classified the variant as Likely Benign via ClinVar (without evidence to independently evaluate). Taken together, this variant is classified as likely benign.
Invitae RCV000237236 SCV000556776 benign Familial hypercholesterolemia 2017-10-05 criteria provided, single submitter clinical testing
LDLR-LOVD, British Heart Foundation RCV000237236 SCV000295119 likely pathogenic Familial hypercholesterolemia 2016-03-25 criteria provided, single submitter literature only
Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde,Academisch Medisch Centrum RCV000237236 SCV000606286 pathogenic Familial hypercholesterolemia no assertion criteria provided research
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000455308 SCV000539505 likely benign not specified 2017-01-24 criteria provided, single submitter clinical testing Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: This variant is present in ExAC with a MaxMAF of 1.3% in African chromosomes - disease prevalence is 1/200-1/300, occurs at greater freq than expected for disorder. It is classified in ClinVar with 1 star as both Likely pathogenic and Likely benign. It has been reported in 6 publications in HGMD but most suggest that it is not pathogenic.
Laboratory of Genetics and Molecular Cardiology,University of São Paulo RCV000237236 SCV000588536 uncertain significance Familial hypercholesterolemia 2016-03-01 criteria provided, single submitter research
U4M - Lille University & CHRU Lille, Université de Lille - CHRU de Lille RCV000237236 SCV000583771 pathogenic Familial hypercholesterolemia 2017-03-30 criteria provided, single submitter clinical testing

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