Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| LDLR- |
RCV000238315 | SCV000295326 | likely pathogenic | Hypercholesterolemia, familial, 1 | 2016-03-25 | criteria provided, single submitter | literature only | |
| Molecular Genetics Laboratory, |
RCV000238315 | SCV000540806 | likely pathogenic | Hypercholesterolemia, familial, 1 | 2016-11-05 | criteria provided, single submitter | clinical testing | |
| Laboratory of molecular diagnosis of dyslipidemias, |
RCV000238315 | SCV001653630 | likely pathogenic | Hypercholesterolemia, familial, 1 | 2021-05-24 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV005090231 | SCV005838543 | likely pathogenic | Familial hypercholesterolemia | 2024-10-02 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with proline, which is neutral and non-polar, at codon 416 of the LDLR protein (p.Arg416Pro). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of familial hypercholesterolemia (PMID: 11317362, 22698793, 23375686, 34297352). This variant is also known as R395P. ClinVar contains an entry for this variant (Variation ID: 251753). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt LDLR protein function with a positive predictive value of 95%. This variant disrupts the p.Arg416 amino acid residue in LDLR. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 9104431, 9259195, 11196104, 11668640, 14974088, 17539906, 18700895, 20538126, 20663204, 21310417, 21376320, 23375686, 25378237, 25921077, 25962062, 26892515). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |
| Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde, |
RCV000238315 | SCV000606374 | pathogenic | Hypercholesterolemia, familial, 1 | no assertion criteria provided | research |