Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000649573 | SCV000771402 | uncertain significance | Charcot-Marie-Tooth disease axonal type 2O | 2017-11-28 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals with DYNC1H1-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces asparagine with threonine at codon 3185 of the DYNC1H1 protein (p.Asn3185Thr). The asparagine residue is highly conserved and there is a small physicochemical difference between asparagine and threonine. 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 and their clinical significance is uncertain. 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. |
| Gene |
RCV001572193 | SCV001796792 | uncertain significance | not provided | 2019-08-20 | criteria provided, single submitter | clinical testing | Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |