Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000549432 | SCV000644801 | uncertain significance | Amyotrophic lateral sclerosis type 1; Perry syndrome; Neuronopathy, distal hereditary motor, type 7B | 2023-04-18 | criteria provided, single submitter | clinical testing | This variant is present in population databases (rs566433112, gnomAD 0.02%). This sequence change replaces lysine, which is basic and polar, with arginine, which is basic and polar, at codon 56 of the DCTN1 protein (p.Lys56Arg). This missense change has been observed in individual(s) with progressive supranuclear palsy (PMID: 27132499). 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. Experimental studies have shown that this missense change affects DCTN1 function (PMID: 27132499). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt DCTN1 protein function. ClinVar contains an entry for this variant (Variation ID: 264686). |