Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001234238 | SCV001406873 | uncertain significance | Amyotrophic lateral sclerosis type 1; Perry syndrome; Neuronopathy, distal hereditary motor, type 7B | 2022-11-29 | 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 missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 960668). This variant has not been reported in the literature in individuals affected with DCTN1-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.002%). This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1253 of the DCTN1 protein (p.Ala1253Val). |
Ambry Genetics | RCV002348787 | SCV002623014 | uncertain significance | Inborn genetic diseases | 2020-10-29 | criteria provided, single submitter | clinical testing | The p.A1253V variant (also known as c.3758C>T), located in coding exon 32 of the DCTN1 gene, results from a C to T substitution at nucleotide position 3758. The alanine at codon 1253 is replaced by valine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. 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. |
Prevention |
RCV003918792 | SCV004733044 | uncertain significance | DCTN1-related disorder | 2023-10-30 | criteria provided, single submitter | clinical testing | The DCTN1 c.3758C>T variant is predicted to result in the amino acid substitution p.Ala1253Val. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0015% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/2-74588705-G-A). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |