Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV001195595 | SCV001365992 | likely pathogenic | Chorea-acanthocytosis | 2019-08-02 | criteria provided, single submitter | clinical testing | The p.Lys752IlefsX9 variant in VPS13A has not been reported in individuals with chorea-acanthocytosis and was absent from large population studies. This variant is predicted to cause a frameshift, which alters the protein’s amino acid sequence beginning at position 752 and leads to a premature termination codon 9 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. Loss of function of the VPS13A gene is an established disease mechanism in autosomal recessive chorea-acanthocytosis. In summary, although additional studies are required to fully establish its clinical significance, this variant meets criteria to be classified as likely pathogenic for autosomal recessive chorea-acanthocytosis. ACMG/AMP criteria applied: PVS1, PM2. |
| Labcorp Genetics |
RCV001863087 | SCV002235198 | pathogenic | not provided | 2021-05-31 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals with VPS13A-related conditions. ClinVar contains an entry for this variant (Variation ID: 930135). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Lys752Ilefs*9) in the VPS13A gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in VPS13A are known to be pathogenic (PMID: 12404112, 21598378). |