Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001896003 | SCV002157381 | uncertain significance | Amyotrophic lateral sclerosis type 1; Perry syndrome; Neuronopathy, distal hereditary motor, type 7B | 2023-11-27 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 502 of the DCTN1 protein (p.Arg502His). This variant is present in population databases (rs780066070, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with DCTN1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1384445). 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 with a negative predictive value of 80%. 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. |
| Ambry Genetics | RCV003166918 | SCV003863553 | uncertain significance | Inborn genetic diseases | 2023-04-28 | criteria provided, single submitter | clinical testing | The c.1505G>A (p.R502H) alteration is located in exon 14 (coding exon 14) of the DCTN1 gene. This alteration results from a G to A substitution at nucleotide position 1505, causing the arginine (R) at amino acid position 502 to be replaced by a histidine (H). Based on data from gnomAD, the A allele has an overall frequency of 0.002% (5/251300) total alleles studied. The highest observed frequency was 0.006% (1/16254) of African alleles. This amino acid position is well conserved in available vertebrate species. This alteration is predicted to be tolerated by in silico analysis. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |