Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001063755 | SCV001228615 | uncertain significance | Developmental and epileptic encephalopathy, 31 | 2019-12-27 | 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with DNM1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces glycine with arginine at codon 631 of the DNM1 protein (p.Gly631Arg). The glycine residue is moderately conserved and there is a moderate physicochemical difference between glycine and arginine. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003331038 | SCV004038766 | uncertain significance | not specified | 2023-08-21 | criteria provided, single submitter | clinical testing | Variant summary: DNM1 c.1891G>C (p.Gly631Arg) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. 4/4 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 6.6e-06 in 150974 control chromosomes (gnomAD v3.1.2). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.1891G>C in individuals affected with Developmental And Epileptic Encephalopathy, 31 and no experimental evidence demonstrating its impact on protein function have been reported. One ClinVar submitter has assessed the variant since 2014, and classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. |