ClinVar Miner

Submissions for variant NM_000527.5(LDLR):c.1413_1414delinsGGACAT (p.Gln474fs)

dbSNP: rs1555805360
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV003352899 SCV004053896 pathogenic Cardiovascular phenotype 2023-08-23 criteria provided, single submitter clinical testing The c.1413_1414delAGinsGGACAT pathogenic mutation, located in coding exon 10 of the LDLR gene, results from the deletion of two nucleotides and insertion of 6 nucleotides causing a translational frameshift with a predicted alternate stop codon (p.Q474Hfs*63). This variant has been previously reported in a familial hypercholesterolemia (FH) cohort (Pirillo A et al. Atheroscler Suppl, 2017 Oct;29:17-24). 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.
Invitae RCV003581676 SCV004284998 pathogenic Familial hypercholesterolemia 2023-03-20 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. This premature translational stop signal has been observed in individual(s) with clinical features of familial hypercholesterolemia (PMID: 28965616). Information on the frequency of this variant in the gnomAD database is not available, as this variant may be reported differently in the database. This sequence change creates a premature translational stop signal (p.Gln474Hisfs*63) in the LDLR gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in LDLR are known to be pathogenic (PMID: 20809525, 28645073).
Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde, Academisch Medisch Centrum RCV000508848 SCV000606416 pathogenic Hypercholesterolemia, familial, 1 no assertion criteria provided research

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