Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Research Laboratories, |
RCV003110195 | SCV003761536 | pathogenic | Hypercholesterolemia, familial, 1 | 2021-09-28 | criteria provided, single submitter | case-control | The novel His607Asp variant in the LDLR gene was identified in a 50yr old female with xanthelasma. The patient has a family history of coronary artery disease. Her Total cholesterol and LDL levels were found to be 357mg/dL and 290mg/dL respectively. The Dutch Lipid score was found to be 11 (Definite FH). This mutation has been found to be pathogenic as per various in silico variant effect prediction tools such as MutationTaster, Mutation assessor, PROVEAN, SIFT and PolyPhen-2, etc. |
All of Us Research Program, |
RCV003110195 | SCV005427624 | uncertain significance | Hypercholesterolemia, familial, 1 | 2024-05-30 | criteria provided, single submitter | clinical testing | This missense variant (also known as p.His586Asp in the mature protein) replaces histidine with aspartic acid at codon 607 of the LDLR protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). 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). 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. |