Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
LDLR- |
RCV000237931 | SCV000295374 | likely pathogenic | Hypercholesterolemia, familial, 1 | 2016-03-25 | criteria provided, single submitter | literature only | |
Gene |
RCV001731460 | SCV001982619 | pathogenic | not provided | 2023-06-09 | criteria provided, single submitter | clinical testing | Located in the conserved YWTD_ motif in a region that is predicted to form a beta-propeller structure (Springer, 1998); the beta propeller and three EGF-like modules constitute the EGF precursor homology domain which is is critical for ligand release and recycling of the receptor (Rudenko et al., 2002; Davis et al., 1987).; In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 11373616, 15199436, 31587492, 7573037, 33740630, 33955087, 12459547, 3494949) |
Color Diagnostics, |
RCV001804976 | SCV002052641 | uncertain significance | Familial hypercholesterolemia | 2023-11-26 | criteria provided, single submitter | clinical testing | This missense variant replaces aspartic acid with glutamic acid at codon 445 of the LDLR protein. This variant is also known as pAsp424Glu in the mature protein, and as FH-Finn-8 in the literature. This variant alters a conserved aspartic acid residue in the LDLR type B repeat 2 of the LDLR protein (a.a. 439 - 485), where pathogenic missense variants are found enriched (ClinVar-LDLR). Computational prediction tools indicate that this variant has a deleterious impact on protein structure and function. One functional study suggested this variant does not affect protein expression, folding, or intracellular trafficking (PMID: 31587492). This variant has been reported in three individuals affected with familial hypercholesterolemia (PMID: 7573037, 15199436, 33740630, 35474963; DOI: 10.1093/eurheartj/ehab724.2566). This variant has been identified in 4/251246 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |