Total submissions: 8
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
LDLR- |
RCV000237602 | SCV000295942 | likely pathogenic | Hypercholesterolemia, familial, 1 | 2016-03-25 | criteria provided, single submitter | literature only | |
Centre de Génétique Moléculaire et Chromosomique, |
RCV000237602 | SCV000503479 | pathogenic | Hypercholesterolemia, familial, 1 | 2016-12-16 | criteria provided, single submitter | clinical testing | subjects mutated among 2600 FH index cases screened = 2 , family member = 1 / FH Italia, 12% LDLR activity |
U4M - |
RCV000237602 | SCV000583941 | pathogenic | Hypercholesterolemia, familial, 1 | 2017-03-30 | criteria provided, single submitter | clinical testing | |
Laboratory of Genetics and Molecular Cardiology, |
RCV000237602 | SCV000588647 | pathogenic | Hypercholesterolemia, familial, 1 | 2016-03-01 | criteria provided, single submitter | research | |
Invitae | RCV001385153 | SCV001584913 | pathogenic | Familial hypercholesterolemia | 2020-05-06 | criteria provided, single submitter | clinical testing | Disruption of this splice site has been observed in individual(s) with familial hypercholesterolemia (PMID: 7545204, 16389549, 20809525). ClinVar contains an entry for this variant (Variation ID: 252274). This variant is not present in population databases (ExAC no frequency). This sequence change affects a donor splice site in intron 15 of the LDLR gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. 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. For these reasons, this variant has been classified as Pathogenic. 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, 28645073). |
Revvity Omics, |
RCV000237602 | SCV002017128 | pathogenic | Hypercholesterolemia, familial, 1 | 2020-03-23 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002446479 | SCV002735337 | pathogenic | Cardiovascular phenotype | 2017-11-27 | criteria provided, single submitter | clinical testing | The c.2311+1G>T intronic pathogenic mutation results from a G to T substitution one nucleotide after coding exon 15 of the LDLR gene. This mutation was reported in two apparently unrelated individuals with familial hypercholesterolemia, and was described to segregate with the disease in their families (Marduel M et al. Hum. Mutat., 2010 Nov;31:E1811-24). 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, |
RCV000237602 | SCV000606630 | pathogenic | Hypercholesterolemia, familial, 1 | no assertion criteria provided | research |