Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
LDLR- |
RCV000237756 | SCV000296031 | pathogenic | Hypercholesterolemia, familial, 1 | 2016-03-25 | criteria provided, single submitter | literature only | |
Cardiovascular Research Group, |
RCV000237756 | SCV000323015 | pathogenic | Hypercholesterolemia, familial, 1 | 2016-03-01 | criteria provided, single submitter | research | 0/188 non-FH alleles |
Invitae | RCV001043694 | SCV001207452 | pathogenic | Familial hypercholesterolemia | 2022-02-05 | criteria provided, single submitter | clinical testing | This sequence change affects a donor splice site in intron 17 of the LDLR gene. RNA analysis indicates that disruption of this splice site induces altered splicing and likely disrupts the C-terminus of the protein. This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individuals with familial hypercholesterolemia (PMID: 17765246; Invitae). ClinVar contains an entry for this variant (Variation ID: 252352). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Studies have shown that disruption of this splice site results in skipping of exon 17 and introduces a new termination codon (PMID: 20828696). However the mRNA is not expected to undergo nonsense-mediated decay. For these reasons, this variant has been classified as Pathogenic. |
Human Genome Sequencing Center Clinical Lab, |
RCV001043694 | SCV001434859 | pathogenic | Familial hypercholesterolemia | 2019-02-01 | criteria provided, single submitter | clinical testing | The c.2547+1G>A variant in the LDLR gene disrupts the canonical splice donor site in intron 17 and is predicted to result in abnormal splicing of LDLR mRNA. This variant is absent from general population databases and has been reported in two unrelated individuals with hypercholesterolemia (PMID 17765246). In addition, skipping of exon 17 and a premature codon at aa805 were observed using mRNA extracted from the blood sample of an individual carrying this variant (PMID 20828696). Thus, this c.2547+1G>A variant in the LDLR gene is classified as pathogenic. |
Mayo Clinic Laboratories, |
RCV003480571 | SCV004227685 | likely pathogenic | not provided | 2022-08-17 | criteria provided, single submitter | clinical testing | PM2, PS4_supporting, PVS1_strong |
Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde, |
RCV000237756 | SCV000606667 | pathogenic | Hypercholesterolemia, familial, 1 | no assertion criteria provided | research |