Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002893830 | SCV003658562 | uncertain significance | Inborn genetic diseases | 2022-11-15 | criteria provided, single submitter | clinical testing | The c.1774A>C (p.M592L) alteration is located in exon 16 (coding exon 16) of the DCTN1 gene. This alteration results from a A to C substitution at nucleotide position 1774, causing the methionine (M) at amino acid position 592 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
| Invitae | RCV003777943 | SCV004581137 | uncertain significance | Amyotrophic lateral sclerosis type 1; Perry syndrome; Neuronopathy, distal hereditary motor, type 7B | 2023-08-20 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 2321923). This sequence change replaces methionine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 592 of the DCTN1 protein (p.Met592Leu). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with DCTN1-related conditions. 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 not expected to disrupt DCTN1 protein function. 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. |