Submissions for variant NM_001356.5(DDX3X):c.976C>T (p.Arg326Cys)

dbSNP: rs1555953548

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000624280	SCV000742218	likely pathogenic	Inborn genetic diseases	2017-02-07	criteria provided, single submitter	clinical testing
Genomic Medicine Lab, University of California San Francisco	RCV001007875	SCV001167578	pathogenic	Intellectual disability, X-linked 102	2018-11-08	criteria provided, single submitter	clinical testing
Institute for Genomic Medicine (IGM) Clinical Laboratory, Nationwide Children's Hospital	RCV001007875	SCV001423697	pathogenic	Intellectual disability, X-linked 102	2017-11-28	criteria provided, single submitter	clinical testing	[ACMG/AMP: PS2, PM1, PM2, PM5, PP2, PP3] This alteration is de novo in origin as it was not detected in the submitted parental specimens (identity confirmed) [PS2], is located in a mutational hotspot and/or critical and well-established functional domain [PM1], is absent from or rarely observed in large-scale population databases [PM2], is a novel missense change at an amino residue where a different missense change has been deemed to be pathogenic [PM5], is a missense variant in a gene in which missense variants are a common mechanism of disease [PP2], is predicted to be damaging by multiple functional prediction tools [PP3].
GeneDx	RCV003238786	SCV003936339	pathogenic	not provided	2025-02-24	criteria provided, single submitter	clinical testing	Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 32371413, 2563148, 33004838, 33993884, 34356170, 38058759, 38421120, 37486637, 37236975)
Labcorp Genetics (formerly Invitae), Labcorp	RCV003238786	SCV004642173	pathogenic	not provided	2023-12-07	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 326 of the DDX3X protein (p.Arg326Cys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with X-linked intellectual disability (PMID: 33993884, 34356170). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 521573). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. This variant disrupts the p.Arg326 amino acid residue in DDX3X. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 26235985, 30125339). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
Breakthrough Genomics, Breakthrough Genomics	RCV001007875	SCV005088787	pathogenic	Intellectual disability, X-linked 102	2023-08-08	criteria provided, single submitter	clinical testing	This variant has been previously reported in patients with developmental delay and/or intellectual disability (ID) [PMID: 33993884, 34356170, 33004838, 32371413].