ClinVar Miner

Submissions for variant NM_001005360.2(DNM2):c.1106G>A (p.Arg369Gln) (rs121909089)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory,University of Chicago RCV000145900 SCV000193037 pathogenic Myopathy, centronuclear 2013-02-08 criteria provided, single submitter clinical testing
Invitae RCV000701394 SCV000830194 pathogenic Charcot-Marie-Tooth disease, dominant intermediate B 2019-04-18 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 369 of the DNM2 protein (p.Arg369Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine. This variant is not present in population databases (ExAC no frequency). This variant has been observed to segregate with centronuclear myopathy in several families (PMID: 16227997, 25501959, 26908122) and has been reported in individuals affected with centronuclear myopathy with and without myotonia (PMID: 19130742, 24366529). ClinVar contains an entry for this variant (Variation ID: 7279). 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: "Possibly Damaging"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. Variants that disrupt the p.Arg369 amino acid residue in DNM2 have been observed in affected individuals (PMID: 16227997, 22613877, 25492887, 20817456, 24016602, 20529869, 28676641). This suggests that it is a clinically significant residue, and that other variants that disrupt this residue are likely to be causative of disease. For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000007702 SCV000027903 pathogenic Myopathy, centronuclear, 1 2005-11-01 no assertion criteria provided literature only

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