Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001217647 | SCV001389496 | pathogenic | Familial hypercholesterolemia | 2019-07-10 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in LDLR are known to be pathogenic (PMID: 20809525, 28645073). This variant has been observed in individuals affected with familial hypercholesterolemia (PMID: 11737238). This variant is also known as 2053del14 in the literature. This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Gln686Leufs*26) in the LDLR gene. It is expected to result in an absent or disrupted protein product. |
| Ambry Genetics | RCV003380891 | SCV004087558 | pathogenic | Cardiovascular phenotype | 2023-07-26 | criteria provided, single submitter | clinical testing | The c.2055_2068del14 pathogenic mutation, located in coding exon 14 of the LDLR gene, results from a deletion of 14 nucleotides at nucleotide positions 2055 to 2068, causing a translational frameshift with a predicted alternate stop codon (p.Q686Lfs*26). This variant (also referred to as 2053del14) has been detected in a familial hypercholesterolemia (FH) cohort, and a cohort submitted for FH genetic testing (Descamps OS et al. Eur J Clin Invest, 2001 Nov;31:958-65; Sturm AC et al. JAMA Cardiol, 2021 Aug;6:902-909). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). 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. |