ClinVar Miner

Submissions for variant NM_000527.5(LDLR):c.1171G>A (p.Ala391Thr)

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Total submissions: 25
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Familial Hypercholesterolemia Variant Curation Expert Panel RCV000237576 SCV001960950 benign Hypercholesterolemia, familial, 1 2021-06-23 reviewed by expert panel curation The NM_000527.5(LDLR):c.1171G>A (p.Ala391Thr) variant is classified as Benign for Familial Hypercholesterolemia by applying evidence codes BA1, BS2, BP2 and BP4 as defined by the ClinGen Familial Hypercholesterolemia Expert Panel LDLR-specific variant curation guidelines (https://doi.org/10.1101/2021.03.17.21252755). The supporting evidence is as follows: BA1 - FAF = 0.1752 (17.52%) in African exomes (gnomAD v2.1.1); frequency meets BA1 >0.5% BS2 - Case-level data in VCI indicates this variant is identified in heterozygosity in 1894 normolipidemic individuals, as well as in homozygosity in 58 normolipidemic individuals. BP2 - Case-level data present in VCI indicates this variant has been identified to co-occur with Pathogenic LDLR variants in at least 3 index cases with heterozygous FH phenotype. BP4 - REVEL = 0.309; score is below BP4 threshold of <0.50. splicing evaluation is required. Functional data on splicing not available. A) not on limits B) does not create GT C) no nearby GT.
LDLR-LOVD, British Heart Foundation RCV000237576 SCV000295254 benign Hypercholesterolemia, familial, 1 2016-03-25 criteria provided, single submitter literature only
PreventionGenetics, part of Exact Sciences RCV000241875 SCV000304683 benign not specified criteria provided, single submitter clinical testing
Cardiovascular Research Group, Instituto Nacional de Saude Doutor Ricardo Jorge RCV000237576 SCV000322933 benign Hypercholesterolemia, familial, 1 2016-03-01 criteria provided, single submitter research MAF = 0.10 in normolipidemic controls; MAF = 8,7% in 86 Spanish healthy individuals; 0/200 Brazilian (european ancestry) normolipidemic individuals; 0/100 healthy control individuals; 0/77 healthy control individuals
Cardiovascular Biomarker Research Laboratory, Mayo Clinic RCV000237576 SCV000323101 likely benign Hypercholesterolemia, familial, 1 2016-08-31 criteria provided, single submitter research DLCN criteria >=3.
Illumina Laboratory Services, Illumina RCV000237576 SCV000410531 benign Hypercholesterolemia, familial, 1 2018-03-06 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Robarts Research Institute, Western University RCV000237576 SCV000484696 likely benign Hypercholesterolemia, familial, 1 2019-08-22 criteria provided, single submitter clinical testing
Centre de Génétique Moléculaire et Chromosomique, Unité de génétique de l'Obésité et des Dyslipidémies, APHP, GH Hôpitaux Universitaires Pitié-Salpêtrière / Charles-Foix RCV000237576 SCV000503308 benign Hypercholesterolemia, familial, 1 2016-12-16 criteria provided, single submitter clinical testing subjects mutated among 2600 FH index cases screened = 201 6 being homozygotes / Software predictions: Benign
GeneDx RCV000241875 SCV000520997 benign not specified 2017-01-05 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Molecular Genetics Laboratory, Centre for Cardiovascular Surgery and Transplantation RCV000237576 SCV000540899 benign Hypercholesterolemia, familial, 1 2017-03-22 criteria provided, single submitter clinical testing
Invitae RCV001082380 SCV000556774 benign Familial hypercholesterolemia 2024-02-01 criteria provided, single submitter clinical testing
Laboratory of Genetics and Molecular Cardiology, University of São Paulo RCV000237576 SCV000588559 benign Hypercholesterolemia, familial, 1 2016-03-01 criteria provided, single submitter research
Athena Diagnostics RCV000241875 SCV000614003 likely benign not specified 2017-03-21 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV000237576 SCV000689758 benign Hypercholesterolemia, familial, 1 2017-06-22 criteria provided, single submitter clinical testing
Department of Human Genetics, Laborarztpraxis Dres. Walther, Weindel und Kollegen RCV000237576 SCV000987023 likely benign Hypercholesterolemia, familial, 1 2018-07-23 criteria provided, single submitter clinical testing Due to the increased occurrence of the mutation (>= 5%), this variant is classified as likely benign.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000162023 SCV002048889 benign not provided 2023-11-29 criteria provided, single submitter clinical testing
Ambry Genetics RCV002326922 SCV002633278 benign Cardiovascular phenotype 2016-03-23 criteria provided, single submitter clinical testing This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Cohesion Phenomics RCV001082380 SCV003836762 benign Familial hypercholesterolemia 2023-02-09 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV000237576 SCV004820275 benign Hypercholesterolemia, familial, 1 2024-02-05 criteria provided, single submitter clinical testing
GENinCode PLC RCV001082380 SCV005050212 benign Familial hypercholesterolemia 2022-07-18 criteria provided, single submitter clinical testing
Dept. of Genetics and Pharmacogenomics, Merck Research Labs RCV000162023 SCV000189626 not provided not provided no assertion provided in vitro
Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde, Academisch Medisch Centrum RCV000237576 SCV000606341 benign Hypercholesterolemia, familial, 1 no assertion criteria provided research
Clinical Genetics, Academic Medical Center RCV000241875 SCV001919018 benign not specified no assertion criteria provided clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen RCV000241875 SCV001963329 benign not specified no assertion criteria provided clinical testing
Natera, Inc. RCV001082380 SCV002086410 benign Familial hypercholesterolemia 2019-10-30 no assertion criteria provided clinical testing

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