ClinVar Miner

Submissions for variant NM_000527.5(LDLR):c.2108_2114dup (p.Arg706fs)

dbSNP: rs879255141
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
LDLR-LOVD, British Heart Foundation RCV000237888 SCV000295877 pathogenic Hypercholesterolemia, familial, 1 2016-03-25 criteria provided, single submitter literature only
Invitae RCV001051686 SCV001215854 pathogenic Familial hypercholesterolemia 2023-04-22 criteria provided, single submitter clinical testing ClinVar contains an entry for this variant (Variation ID: 252223). For these reasons, this variant has been classified as Pathogenic. This variant is also known as 2108ins7, 2114ins7, and FsR685. This premature translational stop signal has been observed in individuals with familial hypercholesterolemia (PMID: 11005141, 11313767, 30592178). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Arg706Alafs*13) 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).
Ambry Genetics RCV003372666 SCV004085715 pathogenic Inborn genetic diseases 2023-07-26 criteria provided, single submitter clinical testing The c.2108_2114dupTGCTGGC (p.R706Afs*13) alteration, located in exon 14 (coding exon 14) of the LDLR gene, consists of a duplication of TGCTGGC at position 2108, causing a translational frameshift with a predicted alternate stop codon after 13 amino acids. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). This alteration has been reported in multiple individuals with either a clinical diagnosis of familial hypercholesterolemia (FH) or a probable diagnosis of FH (Khoo, 2000; Pek, 2018). Based on the available evidence, this alteration is classified as pathogenic.

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