Description
This sequence change replaces arginine, which is basic and polar, with proline, which is neutral and non-polar, at codon 350 of the LDLR protein (p.Arg350Pro). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with familial hypercholesterolemia (PMID: 9026534, 19837725; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 226343). 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. Experimental studies have shown that this missense change affects LDLR function (PMID: 15100232). This variant disrupts the p.Arg350 amino acid residue in LDLR. Other variant(s) that disrupt this residue have been observed in individuals with LDLR-related conditions (PMID: 31106925), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic.
# | Sample | Method | Observation |
---|
Origin | Affected | Number tested | Tissue | Purpose | Method | Individuals | Allele frequency | Families | Co-occurrences |
---|
1 | germline | unknown | not provided | not provided | not provided | | not provided | not provided | not provided | not provided |