ClinVar Miner

Submissions for variant NM_000527.5(LDLR):c.2180_2184dup (p.Leu729fs)

dbSNP: rs1555808044
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Molecular Genetics Laboratory, Centre for Cardiovascular Surgery and Transplantation RCV000454988 SCV000540864 pathogenic Hypercholesterolemia, familial, 1 2016-11-05 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000800880 SCV000940622 pathogenic Familial hypercholesterolemia 2018-08-20 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Leu729Serfs*3) in the LDLR gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed in an individual affected with familial hypercholesterolemia (PMID: 28379029). This variant is also known as c.2184insTCAGG in the literature. ClinVar contains an entry for this variant (Variation ID: 403646). Loss-of-function variants in LDLR are known to be pathogenic (PMID: 20809525). For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics RCV002429465 SCV002730109 pathogenic Cardiovascular phenotype 2018-01-19 criteria provided, single submitter clinical testing The c.2180_2184dupTCAGG pathogenic mutation, located in coding exon 15 of the LDLR gene, results from a duplication of TCAGG at nucleotide position 2180, causing a translational frameshift with a predicted alternate stop codon (p.L729Sfs*3). This alteration, referred to as c.2184insTCAGG, was reported in an individual from a hypercholesterolemia cohort (Tichý L et al. Physiol Res, 2017 Apr;66:S47-S54). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.

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