Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
LDLR- |
RCV000237596 | SCV000295696 | likely pathogenic | Familial hypercholesterolemia 1 | 2016-03-25 | criteria provided, single submitter | literature only | |
Centre de Génétique Moléculaire et Chromosomique, |
RCV000237596 | SCV000503422 | likely pathogenic | Familial hypercholesterolemia 1 | 2016-12-16 | criteria provided, single submitter | clinical testing | subject mutated among 2600 FH index cases screened = 1 |
Iberoamerican FH Network | RCV000237596 | SCV000748155 | uncertain significance | Familial hypercholesterolemia 1 | 2016-03-01 | criteria provided, single submitter | research | |
Invitae | RCV001034634 | SCV000752417 | pathogenic | Familial hypercholesterolemia | 2019-08-07 | criteria provided, single submitter | clinical testing | This sequence change affects codon 615 of the LDLR mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the LDLR protein. This variant also falls at the last nucleotide of exon 12 of the LDLR coding sequence, which is part of the consensus splice site for this exon. This variant is not present in population databases (ExAC no frequency). This variant has been observed in several individuals affected with familial hypercholesterolemia (PMID: 17539906, Invitae). This variant is also known as IVS13-2G>A in the literature. ClinVar contains an entry for this variant (Variation ID: 252065). Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). 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. |
Color | RCV001034634 | SCV001355016 | uncertain significance | Familial hypercholesterolemia | 2018-12-01 | criteria provided, single submitter | clinical testing |