Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Institute of Human Genetics, |
RCV002468570 | SCV002765093 | pathogenic | Hypercholesterolemia, familial, 1 | 2022-11-30 | criteria provided, single submitter | clinical testing | _x000D_ Criteria applied: PS3, PS4_MOD, PM1, PM5, PM2_SUP, PP4 |
All of Us Research Program, |
RCV002468570 | SCV004842631 | uncertain significance | Hypercholesterolemia, familial, 1 | 2023-12-13 | criteria provided, single submitter | clinical testing | This missense variant replaces aspartic acid with glycine at codon 131 of the LDLR protein. This variant is also known as p.Asp110Gly in the mature protein. This variant alters a conserved aspartic acid residue in the LDLR type A repeat 3 of the ligand binding domain of the LDLR protein (a.a. 107 - 145), where pathogenic missense variants are found enriched (ClinVar-LDLR). Computational prediction suggests that this variant may have a deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). A high-throughput functional study has shown that this variant causes a reduction in LDL uptake and localization within the endoplasmic reticulum (PMID: 25647241). This variant has been reported in an individual affected with familial hypercholesterolemia who experienced an early onset myocardial infarction (PMID: 25647241). It was also reported in an individual affected with coronary artery disease (PMID: 27050191) and in a second individual affected with myocardial infarction (PMID: 25487149). This variant has been identified in 2/251190 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Although there is a suspicion that p.Asp131Gly may be associated with disease, additional studies are necessary to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |
Dept. |
RCV000161955 | SCV000189530 | not provided | not provided | no assertion provided | in vitro |