Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000644474 | SCV000766172 | uncertain significance | Amyotrophic lateral sclerosis type 1; Perry syndrome; Neuronopathy, distal hereditary motor, type 7B | 2023-10-22 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 595 of the DCTN1 protein (p.Ser595Asn). 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. ClinVar contains an entry for this variant (Variation ID: 536157). 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. |
| Mayo Clinic Laboratories, |
RCV002261151 | SCV002541845 | uncertain significance | not provided | 2021-09-16 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003235324 | SCV003933737 | uncertain significance | not specified | 2023-05-22 | criteria provided, single submitter | clinical testing | Variant summary: DCTN1 c.1784G>A (p.Ser595Asn) results in a conservative amino acid change located in the Dynein associated protein domain (IPR022157) of the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant was absent in 251496 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.1784G>A in individuals affected with DCTN1-Related Disorders and no experimental evidence demonstrating its impact on protein function have been reported. Two ClinVar submitters (evaluation after 2014) have cited the variant, and both submitters classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. |