ClinVar Miner

Submissions for variant NM_000527.4(LDLR):c.1837G>A (p.Val613Ile) (rs148181903)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CSER_CC_NCGL; University of Washington Medical Center RCV000148595 SCV000190310 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 RCV000210230 SCV000266314 likely benign Familial hypercholesterolemia 2015-08-31 criteria provided, single submitter research MAF =<0.3%
Color RCV000771315 SCV000903571 likely benign Familial hypercholesterolemias 2018-03-14 criteria provided, single submitter clinical testing
Invitae RCV000771315 SCV000945773 uncertain significance Familial hypercholesterolemias 2018-10-02 criteria provided, single submitter clinical testing This sequence change replaces valine with isoleucine at codon 613 of the LDLR protein (p.Val613Ile). The valine residue is weakly conserved and there is a small physicochemical difference between valine and isoleucine. This variant is present in population databases (rs148181903, ExAC 0.01%). This variant has been observed in individuals affected with hypercholesterolemia (PMID: 16250003, 19837725). ClinVar contains an entry for this variant (Variation ID: 161288). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The isoleucine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
LDLR-LOVD, British Heart Foundation RCV000210230 SCV000295691 likely benign Familial hypercholesterolemia 2016-03-25 criteria provided, single submitter literature only
Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde,Academisch Medisch Centrum RCV000210230 SCV000606532 pathogenic Familial hypercholesterolemia no assertion criteria provided research
Laboratory of Genetics and Molecular Cardiology,University of São Paulo RCV000210230 SCV000588610 uncertain significance Familial hypercholesterolemia 2016-03-01 criteria provided, single submitter research

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