Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000554751 | SCV000626046 | uncertain significance | Dystonic disorder | 2017-05-24 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (ExAC no frequency). This sequence change replaces asparagine with aspartic acid at codon 603 of the ANO3 protein (p.Asn603Asp). The asparagine residue is highly conserved and there is a small physicochemical difference between asparagine and aspartic acid. This variant has not been reported in the literature in individuals with a ANO3-related disease. In summary, this variant has uncertain impact on ANO3 function. The available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). |
| Neuberg Centre For Genomic Medicine, |
RCV003338647 | SCV004047983 | uncertain significance | Dystonia 24 | criteria provided, single submitter | clinical testing | The missense variant c.1807A>G(p.Asn603Asp) has been submitted to ClinVar as a Variant of Uncertain Significance (VUS), but no details are available for independent assessment. The p.Asn603Asp variant is novel (not in any individuals) in gnomAD Exomes and 1000 Genomes. The amino acid change p.Asn603Asp in ANO3 is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. The amino acid Asn at position 603 is changed to a Asp changing protein sequence and it might alter its composition and physicochemical properties. For these reasons, this variant has been classified as Uncertain Significance (VUS) |