ClinVar Miner

Submissions for variant NM_000527.4(LDLR):c.1463T>C (p.Ile488Thr) (rs879254913)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Cardiovascular Research Group,Instituto Nacional de Saude Doutor Ricardo Jorge RCV000238089 SCV000322955 likely pathogenic Familial hypercholesterolemia 2016-03-01 criteria provided, single submitter research 0/208 non-FH alleles
Invitae RCV000238089 SCV000823891 uncertain significance Familial hypercholesterolemia 2018-03-14 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with threonine at codon 488 of the LDLR protein (p.Ile488Thr). The isoleucine residue is highly conserved and there is a moderate physicochemical difference between isoleucine and threonine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in an individual affected with hypercholesterolemia (PMID: 11810272). ClinVar contains an entry for this variant (Variation ID: 251857). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). Different missense substitutions at this codon have been reported in individuals affected with hypercholesterolemia (PMID: 23375686, 10978268, 20236128). 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 RCV000238089 SCV000295448 likely pathogenic Familial hypercholesterolemia 2016-03-25 criteria provided, single submitter literature only
Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde,Academisch Medisch Centrum RCV000238089 SCV000606434 pathogenic Familial hypercholesterolemia no assertion criteria provided research
Laboratory of Genetics and Molecular Cardiology,University of São Paulo RCV000238089 SCV000588580 likely pathogenic Familial hypercholesterolemia 2016-03-01 criteria provided, single submitter research

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