Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000553770 | SCV000644827 | uncertain significance | Amyotrophic lateral sclerosis type 1; Perry syndrome; Neuronopathy, distal hereditary motor, type 7B | 2016-08-30 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a DCTN1-related disease. In summary, this variant is a novel missense change that is not predicted to affect protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies.The threonine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. This sequence change replaces alanine with threonine at codon 126 of the DCTN1 protein (p.Ala126Thr). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and threonine. |