Total submissions: 8
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
LDLR- |
RCV000238115 | SCV000295983 | pathogenic | Hypercholesterolemia, familial, 1 | 2016-03-25 | criteria provided, single submitter | literature only | |
Invitae | RCV001828123 | SCV000544639 | pathogenic | Familial hypercholesterolemia | 2023-06-04 | criteria provided, single submitter | clinical testing | This variant is present in population databases (rs767790696, gnomAD 0.0009%). This sequence change affects an acceptor splice site in intron 16 of the LDLR gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in LDLR are known to be pathogenic (PMID: 20809525, 28645073). Disruption of this splice site has been observed in individuals with familial hypercholesterolemia (PMID: 8141835, 10441197, 12052488, 16465405, 20145306, 21382890, 22698793). It has also been observed to segregate with disease in related individuals. For these reasons, this variant has been classified as Pathogenic. Studies have shown that disruption of this splice site is associated with altered splicing resulting in unknown protein product impact (PMID: 8141835). ClinVar contains an entry for this variant (Variation ID: 252313). |
Fundacion Hipercolesterolemia Familiar | RCV000238115 | SCV000607701 | pathogenic | Hypercholesterolemia, familial, 1 | 2016-03-01 | criteria provided, single submitter | research | |
Robarts Research Institute, |
RCV000238115 | SCV000782940 | pathogenic | Hypercholesterolemia, familial, 1 | 2018-01-02 | criteria provided, single submitter | clinical testing | |
Brunham Lab, |
RCV000238115 | SCV001432636 | pathogenic | Hypercholesterolemia, familial, 1 | 2019-06-05 | criteria provided, single submitter | research | |
Ambry Genetics | RCV002450749 | SCV002737105 | pathogenic | Cardiovascular phenotype | 2019-01-07 | criteria provided, single submitter | clinical testing | The c.2390-2A>G intronic pathogenic mutation (also known as IVS16-2A>G) results from an A to G substitution two nucleotides upstream from coding exon 17 in the LDLR gene. This alteration has been reported in multiple familial hypercholesterolemia (FH) cohorts and functional studies have shown this alteration to have an impact on splicing (Lombardi P et al. Atherosclerosis, 1993 Dec;104:117-28; Peeters AV et al. Mol. Cell. Probes, 1999 Aug;13:257-60; Alonso R et al. Clin. Biochem., 2009 Jun;42:899-903; Chmara M et al. J. Appl. Genet., 2010;51:95-106; Lind S et al. Atherosclerosis, 2002 Aug;163:399-407; van der Graaf A et al. Circulation, 2011 Mar;123:1167-73). In addition to the clinical data presented in the literature, alterations that disrupt the canonical splice site are expected to cause aberrant splicing, resulting in an abnormal protein or a transcript that is subject to nonsense-mediated mRNA decay. As such, this alteration is classified as a disease-causing mutation. |
Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde, |
RCV000238115 | SCV000606639 | pathogenic | Hypercholesterolemia, familial, 1 | no assertion criteria provided | research | ||
Natera, |
RCV001828123 | SCV002086877 | pathogenic | Familial hypercholesterolemia | 2021-01-05 | no assertion criteria provided | clinical testing |