Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory of molecular diagnosis of dyslipidemias, |
RCV000700931 | SCV001653606 | pathogenic | Hypercholesterolemia, familial, 1 | 2021-05-24 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV002233349 | SCV000829708 | pathogenic | Familial hypercholesterolemia | 2018-04-16 | criteria provided, single submitter | clinical testing | Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in LDLR are known to be pathogenic (PMID: 20809525). This sequence change affects a donor splice site in intron 4 of the LDLR gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with LDLR-related disease. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. Other substitutions at this nucleotide (c.694+1G>A, c.694+1G>T) have been reported in individuals affected with hypercholesterolemia (PMID: 16542394, 20809525). For these reasons, this variant has been classified as Pathogenic. |