ClinVar Miner

Submissions for variant NM_004408.4(DNM1):c.443A>G (p.Gln148Arg)

dbSNP: rs1554772959
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000653150 SCV000775026 likely pathogenic Developmental and epileptic encephalopathy, 31A 2017-09-20 criteria provided, single submitter clinical testing This sequence change replaces glutamine with arginine at codon 148 of the DNM1 protein (p.Gln148Arg). The glutamine residue is highly conserved and there is a small physicochemical difference between glutamine and arginine. This variant is not present in population databases (ExAC no frequency). This variant has been reported to be de novo in individuals affected with epilepsy, psychomotor retardation and hypotonia (PMID: 27806796 [Paper in Chinese]). 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, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
DASA RCV000653150 SCV002073772 likely pathogenic Developmental and epileptic encephalopathy, 31A 2022-02-05 criteria provided, single submitter clinical testing The c.443A>G;p.(Gln148Arg) missense variant has been observed in affected individual(s) and ClinVar contains an entry for this variant (Clinvar ID: 542676; PMID: 27806796; 31920647) - PS4_supporting. This variant is not present in population databases (rs1554772959; gnomAD; ABraOM no frequency - http://abraom.ib.usp.br/) - PM2. Pathogenic missense variant in this residue have been reported (Clivar ID: 495249- c.442C>A (p.Gln148Lys)) - PM5. Missense variant in DNM1 that has a low rate of benign missense variation and in which missense variants are a common mechanism of disease - PP2. Multiple lines of computational evidence support a deleterious effect on the gene or gene product - PP3. In summary, the currently available evidence indicates that the variant is likely pathogenic.

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