ClinVar Miner

Submissions for variant NM_000527.5(LDLR):c.1706-10G>A

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Total submissions: 28
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Familial Hypercholesterolemia Variant Curation Expert Panel RCV000211645 SCV002506376 likely benign Hypercholesterolemia, familial, 1 2022-03-16 reviewed by expert panel curation The NM_000527.5(LDLR):c.1706-10G>A variant is classified as Likely benign for Familial Hypercholesterolemia by applying evidence codes BS1, BS3_supporting and PP1_moderate as defined by the ClinGen Familial Hypercholesterolemia Expert Panel LDLR-specific variant curation guidelines (https://doi.org/10.1016/j.gim.2021.09.012). The supporting evidence is as follows: BS1 - FAF = 0.002911 (0.2911%) in Latino/Admixed American exomes (gnomAD v2.1.1), so BS1 is Met. BS3_supporting - 2 Level 3 assays: PMID: 25741862: Heterozygous patients' lymphocytes, RNA assays - result - Normal LDLR transcripts identified by sequencing. PMID: 19208450: Heterozygous patients' Epstein Barr virus transformed lymphocytes, RNA assays - result - Normal LDLR transcripts, 43% of mutant transcripts (from total transcripts) in htz cells. ---- Aberrant transcripts are not detected, so BS3_Supporting is Met. PP1_moderate - Variant segregates with FH phenotype in at least 5 informative meiosis from 2 families from Cardiovascular Research Group, Instituto Nacional de Saude Doutor Ricardo Jorge: 5 affected family members have the variant, so PP1_Moderate is Met. Variant has 1 Strong plus 1 Supporting evidence codes towards Benign, enough to classify as Likely benign and only 1 Moderate evidence code towards Pathogenic, not enough for Likely pathogenic, so we are confident in classifying this variant as Likely benign.
LDLR-LOVD, British Heart Foundation RCV000211645 SCV000295599 likely benign Hypercholesterolemia, familial, 1 2016-03-25 criteria provided, single submitter literature only
Cardiovascular Research Group, Instituto Nacional de Saude Doutor Ricardo Jorge RCV000211645 SCV000322971 likely benign Hypercholesterolemia, familial, 1 2016-03-01 criteria provided, single submitter research 1/125 non-FH individuals
Cardiovascular Biomarker Research Laboratory, Mayo Clinic RCV000211645 SCV000323103 uncertain significance Hypercholesterolemia, familial, 1 2016-08-31 criteria provided, single submitter research MAF =<0.3%, LDL-C >=160 mg/dL
Centre de Génétique Moléculaire et Chromosomique, Unité de génétique de l'Obésité et des Dyslipidémies, APHP, GH Hôpitaux Universitaires Pitié-Salpêtrière / Charles-Foix RCV000211645 SCV000503394 benign Hypercholesterolemia, familial, 1 2016-12-16 criteria provided, single submitter clinical testing subjects mutated among 2600 FH index cases screened = 15
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000455738 SCV000539506 likely benign not specified 2017-02-03 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 is an intronic variant in LDLR. It is classified as DM? in HGMD. It has been reported in 2 probands with hypercholesterolemia but in both co-occurred with another variant. It is classified in ClinVar with 1 star as Benign by Cardiovascular Genetics Laboratory,PathWest Laboratory Medicine WA - Fiona Stanley Hospital, Likely benign by British Heart Foundation and Instituto Nacional de Saude Doutor Ricardo Jorge (in 1/125 non-FH individuals), and as VUS by CHOP. It has a max MAF in ExAC of 0.38% (44 Latino alleles) and in gnomAD of 0.4% (41 Ashkenazi and 122 Latino alleles).
Invitae RCV000771093 SCV000556772 benign Familial hypercholesterolemia 2024-01-31 criteria provided, single submitter clinical testing
U4M - Lille University & CHRU Lille, Université de Lille - CHRU de Lille RCV000211645 SCV000583867 likely benign Hypercholesterolemia, familial, 1 2017-03-30 criteria provided, single submitter clinical testing
Laboratory of Genetics and Molecular Cardiology, University of São Paulo RCV000211645 SCV000588603 likely benign Hypercholesterolemia, familial, 1 2016-03-01 criteria provided, single submitter research
Fundacion Hipercolesterolemia Familiar RCV000211645 SCV000607628 likely benign Hypercholesterolemia, familial, 1 2016-03-01 criteria provided, single submitter research
Color Diagnostics, LLC DBA Color Health RCV000771093 SCV000689765 benign Familial hypercholesterolemia 2022-01-19 criteria provided, single submitter clinical testing
GeneDx RCV000455738 SCV000730511 benign not specified 2017-12-04 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.
Iberoamerican FH Network RCV000211645 SCV000748152 likely benign Hypercholesterolemia, familial, 1 2016-03-01 criteria provided, single submitter research
Robarts Research Institute, Western University RCV000211645 SCV000782923 likely benign Hypercholesterolemia, familial, 1 2018-01-02 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000759075 SCV000888162 benign not provided 2022-05-26 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV000771093 SCV000902688 benign Familial hypercholesterolemia 2018-06-28 criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV000211645 SCV001281863 uncertain significance Hypercholesterolemia, familial, 1 2018-08-28 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. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
CeGaT Center for Human Genetics Tuebingen RCV000759075 SCV001747208 likely benign not provided 2022-06-01 criteria provided, single submitter clinical testing LDLR: BP4, BS1
Ambry Genetics RCV002399781 SCV002712874 benign Cardiovascular phenotype 2021-09-28 criteria provided, single submitter clinical testing This alteration is classified as benign based on a combination of the following: 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.
Fulgent Genetics, Fulgent Genetics RCV000211645 SCV002804653 likely benign Hypercholesterolemia, familial, 1 2022-04-28 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000759075 SCV004564798 benign not provided 2023-11-08 criteria provided, single submitter clinical testing
Cardiovascular Genetics Laboratory, PathWest Laboratory Medicine WA - Fiona Stanley Hospital RCV000211645 SCV000268631 benign Hypercholesterolemia, familial, 1 2015-04-02 no assertion criteria provided clinical testing
Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia RCV000211645 SCV000296925 uncertain significance Hypercholesterolemia, familial, 1 2015-09-02 flagged submission clinical testing
Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde, Academisch Medisch Centrum RCV000211645 SCV000606493 benign Hypercholesterolemia, familial, 1 no assertion criteria provided research
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen RCV000211645 SCV000733826 likely benign Hypercholesterolemia, familial, 1 no assertion criteria provided clinical testing
Clinical Genetics, Academic Medical Center RCV000455738 SCV001922575 benign not specified no assertion criteria provided clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center RCV000759075 SCV001975804 likely benign not provided no assertion criteria provided clinical testing
Natera, Inc. RCV000771093 SCV002086435 likely benign Familial hypercholesterolemia 2019-11-06 no assertion criteria provided clinical testing

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