ClinVar Miner

Submissions for variant NM_000527.5(LDLR):c.1988-5C>G

gnomAD frequency: 0.00006  dbSNP: rs375877599
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
LDLR-LOVD, British Heart Foundation RCV000237116 SCV000295798 uncertain significance Hypercholesterolemia, familial, 1 2016-03-25 criteria provided, single submitter literature only
Color Diagnostics, LLC DBA Color Health RCV000776246 SCV000911497 likely benign Familial hypercholesterolemia 2017-07-06 criteria provided, single submitter clinical testing
Invitae RCV000776246 SCV001010946 benign Familial hypercholesterolemia 2024-01-11 criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV000237116 SCV001286048 uncertain significance Hypercholesterolemia, familial, 1 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Ambry Genetics RCV002418059 SCV002719089 likely benign Cardiovascular phenotype 2023-06-26 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
GeneDx RCV003105835 SCV003761835 uncertain significance not provided 2023-01-24 criteria provided, single submitter clinical testing Identified in association with FH (Humphries et al., 2006); In silico analysis suggests this variant may impact gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown.; This variant is associated with the following publications: (PMID: 16389549, 34040191)
Quest Diagnostics Nichols Institute San Juan Capistrano RCV003105835 SCV004219967 uncertain significance not provided 2023-09-15 criteria provided, single submitter clinical testing In the published literature, this variant has been reported in individuals affected with hypercholesterolemia (PMIDs: 16389549 (2006), 20236128 (2010), 34040191 (2021)). The frequency of this variant in the general population, 0.0014 (14/10076 chromosomes in Ashkenazi Jewish subpopulation (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is higher than would generally be expected for pathogenic variants in this gene. Analysis of this variant using software algorithms for the prediction of the effect of nucleotide changes on LDLR mRNA splicing yielded inconclusive findings . Based on the available information, we are unable to determine the clinical significance of this variant.

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