ClinVar Miner

Submissions for variant NM_000527.4(LDLR):c.337G>A (p.Glu113Lys) (rs769383881)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Fundacion Hipercolesterolemia Familiar RCV000232879 SCV000607448 likely pathogenic Familial hypercholesterolemia 2016-03-01 criteria provided, single submitter research
Invitae RCV000232879 SCV000285029 likely pathogenic Familial hypercholesterolemia 2018-02-08 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with lysine at codon 113 of the LDLR protein (p.Glu113Lys). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and lysine. This variant is present in population databases (rs769383881, ExAC <0.01%). This variant has been reported to segregate with elevated LDL levels in a single family (PMID: 10807540). It has also been reported in several unrelated individuals affected with hypercholesterolemia (PMID: 16250003, 17539906, Invitae). This variant is also known as E92K in the literature. ClinVar contains an entry for this variant (Variation ID: 237872). 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: "Possibly Damaging"; Align-GVGD: "Class C0"). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
LDLR-LOVD, British Heart Foundation RCV000232879 SCV000294636 uncertain significance Familial hypercholesterolemia 2016-03-25 criteria provided, single submitter literature only
Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde,Academisch Medisch Centrum RCV000232879 SCV000606089 pathogenic Familial hypercholesterolemia no assertion criteria provided research

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