Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001346090 | SCV001540263 | uncertain significance | Amyotrophic lateral sclerosis type 1; Perry syndrome; Neuronopathy, distal hereditary motor, type 7B | 2023-11-24 | 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 1173 of the DCTN1 protein (p.Arg1173His). This variant is present in population databases (no rsID available, gnomAD 0.01%). 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: 1042180). 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 | RCV002456499 | SCV002614649 | uncertain significance | Inborn genetic diseases | 2022-04-25 | criteria provided, single submitter | clinical testing | The p.R1173H variant (also known as c.3518G>A), located in coding exon 29 of the DCTN1 gene, results from a G to A substitution at nucleotide position 3518. The arginine at codon 1173 is replaced by histidine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |