Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000535411 | SCV000644797 | uncertain significance | Amyotrophic lateral sclerosis type 1; Perry syndrome; Neuronopathy, distal hereditary motor, type 7B | 2022-08-22 | 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 tolerated. ClinVar contains an entry for this variant (Variation ID: 468257). This variant has not been reported in the literature in individuals affected with DCTN1-related conditions. This variant is present in population databases (rs763480310, gnomAD 0.002%). This sequence change replaces methionine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 442 of the DCTN1 protein (p.Met442Val). |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003323605 | SCV004029851 | uncertain significance | not specified | 2023-07-06 | criteria provided, single submitter | clinical testing | Variant summary: DCTN1 c.1324A>G (p.Met442Val) results in a conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 1.2e-05 in 251490 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.1324A>G has been reported in the literature in at least one individual affected with distal Hereditary Motor Neuronopathy (Antoniadi_2015). This report does not provide unequivocal conclusions about association of the variant with DCTN1-Related Disorders. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication has been ascertained in the context of this evaluation (PMID: 26392352). One ClinVar submitter has assessed this variant since 2014, and classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. |