Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| LDLR- |
RCV000237233 | SCV000295056 | likely pathogenic | Hypercholesterolemia, familial, 1 | 2016-03-25 | criteria provided, single submitter | literature only | |
| Centre de Génétique Moléculaire et Chromosomique, |
RCV000237233 | SCV000503254 | likely pathogenic | Hypercholesterolemia, familial, 1 | 2016-12-16 | criteria provided, single submitter | clinical testing | subject mutated among 2600 FH index cases screened = 1 / Software predictions: Conflicting |
| Molecular Genetics Laboratory, |
RCV000237233 | SCV000540771 | likely pathogenic | Hypercholesterolemia, familial, 1 | 2016-11-05 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV000237233 | SCV000544650 | uncertain significance | Hypercholesterolemia, familial, 1 | 2016-05-28 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid with asparagine at codon 307 of the LDLR protein (p.Asp307Asn). The aspartic acid residue is highly conserved and there is a small physicochemical difference between aspartic acid and asparagine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in an individual affected with familial hypercholesterolemia (PMID: 22698793). This variant is also known as p.Asp286Asn in the literature. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). In summary, this variant is a rare missense change with uncertain impact on protein function. While it is absent from the population and reported in an affected individual, the available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
| de |
RCV000237233 | SCV004022253 | likely pathogenic | Hypercholesterolemia, familial, 1 | 2023-07-21 | no assertion criteria provided | research | The variant NM_000527.5:c.919G>A (chr19:11107493) in LDLR was detected in 12 heterozygotes out of 58K WGS Icelanders (MAF= 0,010%). Following imputation in a set of 166K Icelanders (18 imputed heterozygotes) we observed an association with LDL cholesterol using measurements from 128289 individuals (Effect (SD)= 2.53, P= 1.29e-18), Non-HDL cholesterol using measurements from 136901 individuals (Effect (SD)= 2.35, P= 6.00e-17) and myocardial infarction using 25692 cases and 320832 controls (OR= 4.72, P= 3.43e-02). This variant has been reported in ClinVar previously as likely pathogenic and as a variant of uncertain significance. Based on ACMG criteria (PS4, PP1, PP5) this variant classifies as likely pathogenic. |