Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001972752 | SCV002240846 | pathogenic | not provided | 2024-02-07 | criteria provided, single submitter | clinical testing | This sequence change falls in intron 6 of the LPL gene. It does not directly change the encoded amino acid sequence of the LPL protein. RNA analysis indicates that this variant induces altered splicing and likely disrupts the C-terminus of the protein. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individual(s) with chylomicronemia (PMID: 7897314). ClinVar contains an entry for this variant (Variation ID: 1457932). Studies have shown that this variant alters LPL gene expression (PMID: 7897314). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Studies have shown that this variant results in skipping of exons 6-9 and introduces a new termination codon (PMID: 7897314). However the mRNA is not expected to undergo nonsense-mediated decay. For these reasons, this variant has been classified as Pathogenic. |
| Ambry Genetics | RCV002352653 | SCV002660537 | pathogenic | Cardiovascular phenotype | 2021-07-23 | criteria provided, single submitter | clinical testing | The c.1019-3C>A intronic pathogenic mutation results from a C to A substitution 3 nucleotides upstream from coding exon 7 in the LPL gene. This alteration has been reported in three individuals with familial chylomicronemia syndrome (FCS), being identified as homozygous in two of the individuals and suspected compound heterozygous with another known pathogenic alteration, p.G215E (c.644G>A), also known as p.G188E, in one of the individuals (Hölzl B et al. J Lipid Res, 1994 Dec;35:2161-9; Rodrigues R et al. J Clin Lipidol Dec;10:394-409). Additionally, in vitro studies demonstrated that this alteration results in aberrant splicing (Hölzl B et al. J Lipid Res, 1994 Dec;35:2161-9). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). In addition, in silico splice site analysis predicts that this alteration will weaken the native splice acceptor site. Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation. |
| Genomic Medicine Center of Excellence, |
RCV003994365 | SCV004812918 | likely pathogenic | Hyperlipoproteinemia, type I | 2024-03-25 | criteria provided, single submitter | clinical testing |