Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
All of Us Research Program, |
RCV004806746 | SCV005426464 | uncertain significance | Hypercholesterolemia, familial, 1 | 2024-04-16 | criteria provided, single submitter | clinical testing | This variant causes an in-frame deletion of one amino acid (glutamine) and insertion of 5 amino acids (glycine, methionine, aspartic acid, cysteine, and lysine) at codon 228 in exon 4 of the LDLR protein. To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with LDLR-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Multiple different missense variants affecting glutamine at codon 228 (p.Glu228Lys and p.Glu228Gln) are considered to be disease-causing (ClinVar variation ID: 3691 and 251393), suggesting that glutamine at this position is important for LDLR protein function. 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. |