Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000807199 | SCV000947241 | likely pathogenic | Dystonic disorder | 2020-07-21 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (ExAC no frequency). This sequence change replaces asparagine with serine at codon 648 of the ANO3 protein (p.Asn648Ser). The asparagine residue is highly conserved and there is a small physicochemical difference between asparagine and serine. This variant has been observed in individual(s) with dystonia (PMID: 31053532). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 651774). 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: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |
| Institute of Human Genetics Munich, |
RCV003336201 | SCV004045780 | likely pathogenic | Dystonia 24 | 2023-01-30 | criteria provided, single submitter | clinical testing |