Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| LDLR- |
RCV000237903 | SCV000295312 | likely pathogenic | Hypercholesterolemia, familial, 1 | 2016-03-25 | criteria provided, single submitter | literature only | |
| Robarts Research Institute, |
RCV000237903 | SCV000782910 | uncertain significance | Hypercholesterolemia, familial, 1 | 2018-01-02 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV003581617 | SCV004298349 | pathogenic | Familial hypercholesterolemia | 2023-06-25 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Arg410 amino acid residue in LDLR. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 19062533). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Experimental studies have shown that this missense change affects LDLR function (PMID: 27998977). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt LDLR protein function. ClinVar contains an entry for this variant (Variation ID: 251741). This missense change has been observed in individuals with familial hypercholesterolemia (PMID: 23375686, 27998977). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with serine, which is neutral and polar, at codon 410 of the LDLR protein (p.Arg410Ser). |