Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
LDLR- |
RCV000237102 | SCV000295552 | likely pathogenic | Hypercholesterolemia, familial, 1 | 2016-03-25 | criteria provided, single submitter | literature only | |
Iberoamerican FH Network | RCV000237102 | SCV000748057 | likely pathogenic | Hypercholesterolemia, familial, 1 | 2016-03-01 | criteria provided, single submitter | research | |
Invitae | RCV001854904 | SCV002228783 | pathogenic | Familial hypercholesterolemia | 2022-07-19 | criteria provided, single submitter | clinical testing | This variant disrupts the p.Gly546 amino acid residue in LDLR. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 17539906, 22859806; Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 251947). This variant is also known as p.G525V. This missense change has been observed in individuals with familial hypercholesterolemia (PMID: 15823280, 17539906, 21722902). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 546 of the LDLR protein (p.Gly546Val). For these reasons, this variant has been classified as Pathogenic. |