ClinVar Miner

Submissions for variant NM_000527.5(LDLR):c.2242G>A (p.Asp748Asn) (rs150104358)

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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 RCV000237615 SCV000295925 likely benign Familial hypercholesterolemia 1 2016-03-25 criteria provided, single submitter literature only
Illumina Clinical Services Laboratory,Illumina RCV000237615 SCV000410544 uncertain significance Familial hypercholesterolemia 1 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Robarts Research Institute,Western University RCV000237615 SCV000484755 uncertain significance Familial hypercholesterolemia 1 2019-08-22 criteria provided, single submitter clinical testing
Color Health, Inc RCV001178125 SCV001342485 uncertain significance Familial hypercholesterolemia 2019-11-15 criteria provided, single submitter clinical testing
Invitae RCV001178125 SCV001531711 uncertain significance Familial hypercholesterolemia 2020-08-20 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with asparagine at codon 748 of the LDLR protein (p.Asp748Asn). The aspartic acid residue is weakly conserved and there is a small physicochemical difference between aspartic acid and asparagine. This variant is present in population databases (rs150104358, ExAC 0.05%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This variant has been observed in individual(s) with clinical features of LDLR-related conditions (PMID: 25487149, 27765764). ClinVar contains an entry for this variant (Variation ID: 183133). Experimental studies are conflicting or provide insufficient evidence to determine the effect of this variant on LDLR protein function (PMID: 25647241). 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.
Dept. of Genetics and Pharmacogenomics, Merck Research Labs RCV000162012 SCV000189588 not provided not provided no assertion provided in vitro
Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde,Academisch Medisch Centrum RCV000237615 SCV000606618 pathogenic Familial hypercholesterolemia 1 no assertion criteria provided research

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