ClinVar Miner

Submissions for variant NM_000527.5(LDLR):c.1765G>C (p.Asp589His)

dbSNP: rs201971888
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Familial Hypercholesterolemia Variant Curation Expert Panel RCV002505198 SCV002817144 uncertain significance Hypercholesterolemia, familial, 1 2022-08-29 reviewed by expert panel curation The NM_000527.5(LDLR):c.1765G>C (p.Asp589His) variant is classified as Uncertain significance - insufficient evidence for Familial Hypercholesterolemia by applying evidence codes PM2 and BP4 as defined by the ClinGen Familial Hypercholesterolemia Expert Panel LDLR-specific variant curation guidelines (https://doi.org/10.1016/j.gim.2021.09.012). The supporting evidence is as follows: PM2 - PopMax MAF = 0.000008790 (0.0009%) in Non-Finnish European exomes+genomes (gnomAD v2.1.1) BP4 - REVEL = 0.424. It is below 0.5, splicing evaluation needed. Functional data on splicing not available. A) variant not on limits. B) does not create AG or GT Variant is not predicted to alter splicing
Color Diagnostics, LLC DBA Color Health RCV001804889 SCV002052040 uncertain significance Familial hypercholesterolemia 2021-07-27 criteria provided, single submitter clinical testing This missense variant (also known as p.Asp568His in the mature protein) replaces aspartic acid with histidine at codon 589 of the LDLR protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). One high-throughput study suggested this variant has normal function (PMID: 25647241). This variant has been reported in one individual who survived acute myocardial infarction (PMID: 25647241). This variant has been identified in 1/251490 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.
Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center RCV002505198 SCV004807976 uncertain significance Hypercholesterolemia, familial, 1 2024-03-29 criteria provided, single submitter clinical testing
Dept. of Genetics and Pharmacogenomics, Merck Research Labs RCV000162000 SCV000189575 not provided not provided no assertion provided in vitro

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