ClinVar Miner

Submissions for variant NM_004408.4(DNM1):c.709C>T (p.Arg237Trp) (rs760270633)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000263789 SCV000330044 pathogenic not provided 2017-11-02 criteria provided, single submitter clinical testing The R237W missense variant in the DNM1 gene has been reported as a de novo variant withconfirmed parentage in multiple unrelated individuals with infantile onset epileptic encephalopathy(EuroEPINOMICS-RES et al., 2014; Fitzgerald et al., 2015; Nakashima et al., 2016; von Spiczak etal., 2017). The R237W variant is not observed in large population cohorts (Lek et al., 2016). TheR237W variant is a non-conservative amino acid substitution that occurs at a conserved position in the GTPase domain, and in silico analysis predicts this variant is probably damaging to the proteinstructure/function. Therefore, R237W is considered a pathogenic variant, and its presence isconsistent with the diagnosis of a DNM1-related disorder in this patient.
Invitae RCV000170498 SCV000656484 pathogenic Epileptic encephalopathy, early infantile, 31 2019-10-21 criteria provided, single submitter clinical testing This sequence change replaces arginine with tryptophan at codon 237 of the DNM1 protein (p.Arg237Trp). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is not present in population databases (ExAC no frequency). This variant has been reported to be de novo in individuals affected with epileptic encephalopathy (EE) and West syndrome (PMID: 25262651, 26611353, 29314763). It has also been reported in an individual with EE who inherited the variant from an unaffected parent that carried it as a somatic mosaic variant (PMID: 27476654). ClinVar contains an entry for this variant (Variation ID: 280148). 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. For these reasons, this variant has been classified as Pathogenic.
Fulgent Genetics,Fulgent Genetics RCV000170498 SCV000893796 pathogenic Epileptic encephalopathy, early infantile, 31 2018-10-31 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000263789 SCV001248837 pathogenic not provided 2018-07-01 criteria provided, single submitter clinical testing
Laboratory of Molecular Genetics (Pr. Bezieau's lab), CHU de Nantes RCV000263789 SCV001334362 pathogenic not provided 2019-04-15 criteria provided, single submitter clinical testing
OMIM RCV000170498 SCV000222930 pathogenic Epileptic encephalopathy, early infantile, 31 2015-03-12 no assertion criteria provided literature only

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