ClinVar Miner

Submissions for variant NM_000527.5(LDLR):c.970G>A (p.Gly324Ser)

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Total submissions: 18
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
LDLR-LOVD, British Heart Foundation RCV000237236 SCV000295119 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 RCV000237236 SCV000503271 benign Familial hypercholesterolemia 1 2016-12-16 criteria provided, single submitter clinical testing subjects mutated among 2600 FH index cases screened = 2 / Software predictions: Damaging
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.
Invitae RCV000771170 SCV000556776 benign Familial hypercholesterolemia 2020-12-07 criteria provided, single submitter clinical testing
U4M - Lille University & CHRU Lille, Université de Lille - CHRU de Lille RCV000237236 SCV000583771 pathogenic Familial hypercholesterolemia 1 2017-03-30 criteria provided, single submitter clinical testing
Laboratory of Genetics and Molecular Cardiology, University of São Paulo RCV000237236 SCV000588536 uncertain significance Familial hypercholesterolemia 1 2016-03-01 criteria provided, single submitter research
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000455308 SCV000697255 benign not specified 2021-04-05 criteria provided, single submitter clinical testing Variant summary: LDLR c.970G>A (p.Gly324Ser) results in a non-conservative amino acid change located in the EGF-like domain (IPR000742) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.0012 in 282414 control chromosomes, predominantly at a frequency of 0.014 within the African or African-American subpopulation in the gnomAD database, including 2 homozygotes. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 14 fold of the estimated maximal expected allele frequency for a pathogenic variant in LDLR causing Early Onset Coronary Artery Disease phenotype (0.001), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African or African-American origin. Co-occurrences with other pathogenic LDLR variants have been reported (LDLR c.862G>A, p.E288K; LDLR c.1285G>A, p.Val429Met; internal data and Vaca_2011), providing supporting evidence for a benign role. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. 13 ClinVar submitters (evaluation after 2014) cite the variant as uncertain significance (n=2), likely pathogenic (n=1), pathogenic (n=1), likely benign (n=4) and benign (n=5). Based on the evidence outlined above, the variant was classified as benign.
Iberoamerican FH Network RCV000237236 SCV000748045 uncertain significance Familial hypercholesterolemia 1 2016-03-01 criteria provided, single submitter research
Color Health, Inc RCV000771170 SCV000903099 benign Familial hypercholesterolemia 2017-08-29 criteria provided, single submitter clinical testing
Mendelics RCV000237236 SCV001140984 benign Familial hypercholesterolemia 1 2019-05-28 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000237236 SCV001285931 likely benign Familial hypercholesterolemia 1 2019-02-13 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Brunham Lab, Centre for Heart and Lung Innovation,University of British Columbia RCV000237236 SCV001432674 benign Familial hypercholesterolemia 1 2019-05-23 criteria provided, single submitter research
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease,Montreal Heart Institute RCV000455308 SCV001433285 likely benign not specified 2020-05-18 criteria provided, single submitter clinical testing
GeneDx RCV000162021 SCV001826025 likely benign not provided 2020-12-16 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 32719484, 20981092, 12436241, 11810272, 21722902, 11435110, 9544746, 25647241, 26332594, 25487149, 25637381, 22995991)
Dept. of Genetics and Pharmacogenomics, Merck Research Labs RCV000162021 SCV000189624 not provided not provided no assertion provided in vitro
CSER _CC_NCGL, University of Washington RCV000148566 SCV000190279 likely benign Hypercholesterolaemia 2014-06-01 no assertion criteria provided research
Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde,Academisch Medisch Centrum RCV000237236 SCV000606286 pathogenic Familial hypercholesterolemia 1 no assertion criteria provided research
Natera, Inc. RCV000771170 SCV001465007 likely benign Familial hypercholesterolemia 2020-04-03 no assertion criteria provided clinical testing

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