Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV003188051 | SCV003866486 | pathogenic | Cardiovascular phenotype | 2023-02-07 | criteria provided, single submitter | clinical testing | The c.1361_1364delCCCA pathogenic mutation, located in coding exon 10 of the LDLR gene, results from a deletion of 4 nucleotides at nucleotide positions 1361 to 1364, causing a translational frameshift with a predicted alternate stop codon (p.T454Sfs*52). This variant has been detected in an individual with familial hypercholesterolemia (Ambry internal data). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). 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. |
| Labcorp Genetics |
RCV005101179 | SCV005764633 | pathogenic | Familial hypercholesterolemia | 2024-07-30 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Thr454Serfs*52) 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). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with LDLR-related conditions. ClinVar contains an entry for this variant (Variation ID: 2453916). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. |