ClinVar Miner

Submissions for variant NM_000527.5(LDLR):c.118del (p.Ile40fs)

dbSNP: rs879254413
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
LDLR-LOVD, British Heart Foundation RCV000238149 SCV000294474 pathogenic Hypercholesterolemia, familial, 1 2016-03-25 criteria provided, single submitter literature only
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV004017534 SCV004847773 pathogenic Homozygous familial hypercholesterolemia 2019-10-11 criteria provided, single submitter clinical testing The p.Ile40SerfsX166 variant in LDLR has been identified in at least 3 individuals with hypercholesterolemia (Heath 1999, Martin 2016). It was absent from large population studies. This variant is predicted to cause a frameshift, which alters the protein’s amino acid sequence beginning at position 40 and leads to a premature termination codon 166 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. Loss of function of the LDLR gene is an established disease mechanism in autosomal dominant familial hypercholesterolemia. In summary, this variant meets criteria to be classified as pathogenic for autosomal dominant familial hypercholesterolemia. ACMG/AMP Criteria applied: PVS1, PM2, PS4_Supporting.

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