Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Color Diagnostics, |
RCV001192332 | SCV001360364 | uncertain significance | Familial hypercholesterolemia | 2023-04-05 | criteria provided, single submitter | clinical testing | This missense variant (also known as p.Ala676Thr in the mature protein) replaces alanine with threonine at codon 697 of the LDLR protein. 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). 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 been identified in 1/251080 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. |
| Fulgent Genetics, |
RCV000508717 | SCV002812832 | uncertain significance | Hypercholesterolemia, familial, 1 | 2021-09-20 | criteria provided, single submitter | clinical testing | |
| All of Us Research Program, |
RCV000508717 | SCV004818496 | uncertain significance | Hypercholesterolemia, familial, 1 | 2023-05-04 | criteria provided, single submitter | clinical testing | Variant of Uncertain Significance due to insufficient evidence: This missense variant (also known as p.Ala676Thr in the mature protein) replaces alanine with threonine at codon 697 of the LDLR protein. Computational prediction tools and conservation analyses are inconclusive regarding the impact of this variant on the protein function. Computational splicing tools suggest that this variant may not impact RNA splicing. To our knowledge, functional assays have not been performed for this variant nor has this variant been reported in individuals affected with familial hypercholesterolemia in the literature. This variant has been identified in 1/245924 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Available evidence is insufficient to determine the role of this variant in disease conclusively. |
| Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde, |
RCV000508717 | SCV000606595 | pathogenic | Hypercholesterolemia, familial, 1 | no assertion criteria provided | research |