Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001372956 | SCV001569652 | uncertain significance | Amyotrophic lateral sclerosis type 1; Perry syndrome; Neuronopathy, distal hereditary motor, type 7B | 2020-03-17 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals with DCTN1-related conditions. 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. 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant is not present in population databases (ExAC no frequency). This sequence change replaces glycine with valine at codon 67 of the DCTN1 protein (p.Gly67Val). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and valine. |
Gene |
RCV003229051 | SCV003926156 | uncertain significance | not provided | 2023-05-15 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously reported in peer-reviewed literature as pathogenic or benign to our knowledge. However, in an abstract by Dulski et al. (2023), this variant has been reported in a patient with clinical features of Perry syndrome.; This variant is associated with the following publications: (PMID: Dulski_2023[Poster]) |