Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002454646 | SCV002611971 | uncertain significance | Inborn genetic diseases | 2022-03-22 | criteria provided, single submitter | clinical testing | The p.A1099V variant (also known as c.3296C>T), located in coding exon 28 of the DCTN1 gene, results from a C to T substitution at nucleotide position 3296. The alanine at codon 1099 is replaced by valine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Invitae | RCV003099372 | SCV003477068 | uncertain significance | Amyotrophic lateral sclerosis type 1; Perry syndrome; Neuronopathy, distal hereditary motor, type 7B | 2022-09-14 | criteria provided, single submitter | clinical testing | 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. 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. This variant has not been reported in the literature in individuals affected with DCTN1-related conditions. This variant is present in population databases (rs775022141, gnomAD 0.004%). This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1099 of the DCTN1 protein (p.Ala1099Val). |