Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Color Diagnostics, |
RCV001179047 | SCV001343622 | uncertain significance | Familial hypercholesterolemia | 2023-06-22 | criteria provided, single submitter | clinical testing | This missense variant (also known as p.Ala591Val in the mature protein) replaces alanine with valine at codon 612 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 been identified in 2/282842 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. |
| Labcorp Genetics |
RCV001179047 | SCV002173789 | uncertain significance | Familial hypercholesterolemia | 2021-08-13 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine with valine at codon 612 of the LDLR protein (p.Ala612Val). The alanine residue is moderately conserved and there is a small physicochemical difference between alanine and valine. This variant is not present in population databases (ExAC no frequency). This missense change has been observed in individual(s) with clinical features of LDLR-related conditions (Invitae). ClinVar contains an entry for this variant (Variation ID: 440664). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Ai |
RCV002223856 | SCV002503174 | uncertain significance | not provided | 2021-12-23 | criteria provided, single submitter | clinical testing | |
| All of Us Research Program, |
RCV000508951 | SCV004822506 | uncertain significance | Hypercholesterolemia, familial, 1 | 2023-12-13 | criteria provided, single submitter | clinical testing | This missense variant (also known as p.Ala591Val in the mature protein) replaces alanine with valine at codon 612 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 familial hypercholesterolemia in the literature. This variant has been identified in 2/282842 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. |
| Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde, |
RCV000508951 | SCV000606529 | pathogenic | Hypercholesterolemia, familial, 1 | no assertion criteria provided | research |