Submissions for variant NM_001356.5(DDX3X):c.1126C>T (p.Arg376Cys)

dbSNP: rs796052231

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
CeGaT Center for Human Genetics Tuebingen	RCV001310709	SCV001500617	pathogenic	not provided	2020-11-01	criteria provided, single submitter	clinical testing
Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein	RCV000190550	SCV002512327	likely pathogenic	Intellectual disability, X-linked 102	2021-08-23	criteria provided, single submitter	clinical testing	ACMG classification criteria: PS3 supporting, PS4 moderate, PM2 moderate, PM6 strong
Neuberg Centre For Genomic Medicine, NCGM	RCV000190550	SCV004046982	pathogenic	Intellectual disability, X-linked 102		criteria provided, single submitter	clinical testing	The DDX3X c.1126C>T (p.Arg376Cys) variant has been reported in heterozygous state in multiple individuals affected with Mental Retardation, X-Linked 102 (Snijders Blok et al). The p.Arg376Cys variant is novel (not in any individuals) in gnomAD Exomes and 1000 Genomes. It has been submitted to ClinVar with varying interpretation as Pathogenic and Likely pathogenic. The variant is predicted to be damaging by both SIFT and PolyPhen2. The residue is conserved across species. The amino acid Arg at position 376 is changed to a Cys changing protein sequence and it might alter its composition and physico-chemical properties. For these reasons, this variant has been classified as Pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001310709	SCV004299822	pathogenic	not provided	2023-02-22	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects DDX3X function (PMID: 26235985). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. ClinVar contains an entry for this variant (Variation ID: 207813). This missense change has been observed in individual(s) with DDX3X-related conditions (PMID: 26235985, 28135719). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 376 of the DDX3X protein (p.Arg376Cys).
OMIM	RCV000190550	SCV000245431	pathogenic	Intellectual disability, X-linked 102	2015-08-06	no assertion criteria provided	literature only
Dobyns Lab, Seattle Children's Research Institute	RCV000190550	SCV000916339	pathogenic	Intellectual disability, X-linked 102	2019-02-18	no assertion criteria provided	research
University of Washington Center for Mendelian Genomics, University of Washington	RCV001257982	SCV001434795	likely pathogenic	Congenital cerebellar hypoplasia		no assertion criteria provided	research
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV001310709	SCV001807203	pathogenic	not provided		no assertion criteria provided	clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV001310709	SCV001962983	likely pathogenic	not provided		no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV001310709	SCV002037023	pathogenic	not provided		no assertion criteria provided	clinical testing
GeneReviews	RCV000190550	SCV002098132	not provided	Intellectual disability, X-linked 102		no assertion provided	literature only	Recurrent variant, observed de novo in 3 female probands [Snijders Blok et al 2015]