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

dbSNP: rs760270633

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000263789	SCV000330044	pathogenic	not provided	2023-09-10	criteria provided, single submitter	clinical testing	In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Not observed in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 27476654, 29314763, 32827528, 25262651, 26611353, 25533962, 28667181, 29186148, 33726816, 31785789, 33004838, 31440721)
Invitae	RCV000170498	SCV000656484	pathogenic	Developmental and epileptic encephalopathy, 31	2023-08-29	criteria provided, single submitter	clinical testing	This variant is not present in population databases (gnomAD no frequency). For these reasons, this variant has been classified as Pathogenic. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt DNM1 protein function. ClinVar contains an entry for this variant (Variation ID: 280148). This missense change has been observed in individual(s) with epileptic encephalopathy (EE) and West syndrome (PMID: 25262651, 26611353, 29314763). In at least one individual the variant was observed to be de novo. This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 237 of the DNM1 protein (p.Arg237Trp).
Fulgent Genetics, Fulgent Genetics	RCV000170498	SCV000893796	pathogenic	Developmental and epileptic encephalopathy, 31	2018-10-31	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics 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
Ambry Genetics	RCV001265881	SCV001444053	pathogenic	Inborn genetic diseases	2014-11-05	criteria provided, single submitter	clinical testing
Pediatrics, MediClubGeorgia	RCV000170498	SCV001468641	pathogenic	Developmental and epileptic encephalopathy, 31	2021-01-03	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. The variant is absent in population databases. This de novo variant has been reported in individuals affected with epileptic encephalopathy (EE) and West syndrome. It has also been reported in an individual with EE who inherited the variant from an unaffected parent (somatic mosaic). SIFT - deleterious, PolyPhen - Probably Damaging, FATHMM pred - Damaging, MutationAssessor - High, MutationTaster - diseases causing, Provean - Damaging, MetaSVM - Damaging. The parents were also tested - not detected. On Clinvar this variant is submitted as Pathogenic.
OMIM	RCV000170498	SCV000222930	pathogenic	Developmental and epileptic encephalopathy, 31	2015-03-12	no assertion criteria provided	literature only