Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001972752 | SCV002240846 | pathogenic | not provided | 2020-12-09 | criteria provided, single submitter | clinical testing | This variant has been observed in individual(s) with chylomicronemia (PMID: 7897314). For these reasons, this variant has been classified as Pathogenic. Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Studies have shown that this variant results in Exon 6-9 skipping, which introduces a new termination codon (PMID: 7897314). However the mRNA is not expected to undergo nonsense-mediated decay. Studies have shown that this variant alters LPL gene expression (PMID: 7897314). This variant is not present in population databases (ExAC no frequency). 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. |
| 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. |
| Center for Genomic Medicine, |
RCV003994365 | SCV004812918 | likely pathogenic | Hyperlipoproteinemia, type I | 2024-03-25 | criteria provided, single submitter | clinical testing |