ClinVar Miner

Submissions for variant NM_000527.5(LDLR):c.108C>A (p.Asp36Glu)

dbSNP: rs373144619
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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 RCV000238476 SCV000294469 likely pathogenic Hypercholesterolemia, familial, 1 2016-03-25 criteria provided, single submitter literature only
Invitae RCV001854882 SCV002254617 uncertain significance Familial hypercholesterolemia 2021-02-14 criteria provided, single submitter clinical testing This variant has been observed in individual(s) with autosomal dominant familial hypercholesterolemia (PMID: 11810272, 20506408, Invitae). This variant is also known as D15E. ClinVar contains an entry for this variant (Variation ID: 251022). This variant is not present in population databases (ExAC no frequency). This sequence change replaces aspartic acid with glutamic acid at codon 36 of the LDLR protein (p.Asp36Glu). The aspartic acid residue is moderately conserved and there is a small physicochemical difference between aspartic acid and glutamic acid. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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.
Ambry Genetics RCV002446471 SCV002736613 uncertain significance Cardiovascular phenotype 2022-08-18 criteria provided, single submitter clinical testing The p.D36E variant (also known as c.108C>A), located in coding exon 2 of the LDLR gene, results from a C to A substitution at nucleotide position 108. The aspartic acid at codon 36 is replaced by glutamic acid, an amino acid with highly similar properties. This alteration, which is also known as p.D15E, has been reported in a familial hypercholesterolemia (FH) cohort (Fouchier SW et al. Hum Genet, 2001 Dec;109:602-15). This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde, Academisch Medisch Centrum RCV000238476 SCV000606016 benign Hypercholesterolemia, familial, 1 no assertion criteria provided research

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