Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000805454 | SCV000945411 | uncertain significance | Amyotrophic lateral sclerosis type 1; Perry syndrome; Neuronopathy, distal hereditary motor, type 7B | 2022-08-07 | 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 650325). This variant has not been reported in the literature in individuals affected with DCTN1-related conditions. This variant is present in population databases (rs758168607, gnomAD 0.003%). This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 927 of the DCTN1 protein (p.Arg927Trp). |
Ambry Genetics | RCV002440713 | SCV002746276 | uncertain significance | Inborn genetic diseases | 2020-01-13 | criteria provided, single submitter | clinical testing | The p.R927W variant (also known as c.2779C>T), located in coding exon 24 of the DCTN1 gene, results from a C to T substitution at nucleotide position 2779. The arginine at codon 927 is replaced by tryptophan, an amino acid with dissimilar properties. This amino acid position is highly conserved in available vertebrate species. 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. |