ClinVar Miner

Submissions for variant NM_000527.5(LDLR):c.1538G>A (p.Arg513Lys)

gnomAD frequency: 0.00009  dbSNP: rs879254934
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
LDLR-LOVD, British Heart Foundation RCV000238197 SCV000295488 likely benign Hypercholesterolemia, familial, 1 2016-03-25 criteria provided, single submitter literature only
Molecular Genetics Laboratory, Centre for Cardiovascular Surgery and Transplantation RCV000238197 SCV000540823 likely benign Hypercholesterolemia, familial, 1 2016-11-05 criteria provided, single submitter clinical testing
Invitae RCV002518487 SCV003443878 uncertain significance Familial hypercholesterolemia 2021-12-31 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with lysine, which is basic and polar, at codon 513 of the LDLR protein (p.Arg513Lys). This variant is present in population databases (no rsID available, gnomAD 0.006%). This missense change has been observed in individual(s) with clinical features of hypercholesterolemia (Invitae). ClinVar contains an entry for this variant (Variation ID: 251890). 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 lysine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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.
All of Us Research Program, National Institutes of Health RCV000238197 SCV004822472 uncertain significance Hypercholesterolemia, familial, 1 2023-04-03 criteria provided, single submitter clinical testing This missense variant (also known as p.Arg492Lys in the mature protein) replaces arginine with lysine at codon 513 of the LDLR protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with familial hypercholesterolemia (PMID: 22698793). This variant has been identified in 3/251432 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

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