ClinVar Miner

Submissions for variant NM_000527.4(LDLR):c.58G>A (p.Gly20Arg) (rs147509697)

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Total submissions: 13
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CSER_CC_NCGL; University of Washington Medical Center RCV000148577 SCV000190291 uncertain significance Hypercholesterolaemia 2014-06-01 criteria provided, single submitter research Low GERP score may suggest that this variant may belong in a lower pathogenicity class
Cardiovascular Biomarker Research Laboratory,Mayo Clinic RCV000211611 SCV000266321 uncertain significance Familial hypercholesterolemia 2016-02-19 criteria provided, single submitter research MAF =<0.3%. "Little/No effect" on the LDL receptor activity based on experimental validation.
Cardiovascular Genetics Laboratory,PathWest Laboratory Medicine WA - Fiona Stanley Hospital RCV000211611 SCV000268533 uncertain significance Familial hypercholesterolemia 2010-11-29 no assertion criteria provided clinical testing
Cardiovascular Research Group,Instituto Nacional de Saude Doutor Ricardo Jorge RCV000211611 SCV000322872 uncertain significance Familial hypercholesterolemia 2016-03-01 criteria provided, single submitter research 0/190 non-FH alleles; 0/150 normolipidemic chromosomes
Color RCV000771169 SCV000903098 likely benign Familial hypercholesterolemias 2017-05-12 criteria provided, single submitter clinical testing
Dept. of Genetics and Pharmacogenomics, Merck Research Labs RCV000161949 SCV000189524 not provided not provided no assertion provided in vitro
Fundacion Hipercolesterolemia Familiar RCV000211611 SCV000607408 uncertain significance Familial hypercholesterolemia 2016-03-01 criteria provided, single submitter research
GeneDx RCV000609054 SCV000730501 likely benign not specified 2017-04-05 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.
Integrated Genetics/Laboratory Corporation of America RCV000161949 SCV000697241 likely benign not provided 2017-06-12 criteria provided, single submitter clinical testing Variant summary: The LDLR c.58G>A (p.Gly20Arg) variant involves the alteration of a non-conserved nucleotide. 2/4 in silico tools predict a benign outcome for this variant (SNPsandGO not captured due to low reliability index). This variant was found in 121/111864 control chromosomes, predominantly observed in the European (Finnish) subpopulation at a frequency of 0.001982 (9/4540) and European (Non-Finnish) subpopulation at a frequency of 0.001639 (92/56132). These frequencies are slightly higher than the estimated maximal expected allele frequency of a pathogenic LDLR variant (0.0012508), suggesting this is likely a benign polymorphism found primarily in the populations of European origin. This variant has been reported in many patients with familial hypercholesterolemia and myocardial infarction. However, multiple co-occurrences with a pathogenic LDLR variant and lack of co-segregation have been reported in these patients (Tejedor_2011, Komarova_2013, Klancar_2015, and Medeiros_2014). Two functional studies showed that LDLR p.Gly20Arg had comparable function to WT LDLR in total LDL signal, protein expression and localization and LDL particle binding (Thormaehlen_2015, Pavlouskova_2016). Although multiple clinical diagnostic laboratories classified this variant as uncertain significance, three clinical diagnostic laboratories classified thsi variant as benign/likely benign. Taken together, this variant is classified as likely benign.
Invitae RCV000211611 SCV000556775 likely benign Familial hypercholesterolemia 2017-11-30 criteria provided, single submitter clinical testing
LDLR-LOVD, British Heart Foundation RCV000211611 SCV000294427 likely benign Familial hypercholesterolemia 2016-03-25 criteria provided, single submitter literature only
Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde,Academisch Medisch Centrum RCV000211611 SCV000605999 pathogenic Familial hypercholesterolemia no assertion criteria provided research
Molecular Genetics Laboratory,Centre for Cardiovascular Surgery and Transplantation RCV000211611 SCV000540713 benign Familial hypercholesterolemia 2016-11-05 criteria provided, single submitter clinical testing A functional analysis was previously published (Pavloušková et al, 2016). This variant has no effect on LDLR protein function.

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