Submissions for variant NM_001356.5(DDX3X):c.1490C>T (p.Ala497Val)

dbSNP: rs796052236

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV001265760	SCV001443929	pathogenic	Inborn genetic diseases	2015-09-29	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001857666	SCV002232023	pathogenic	not provided	2021-12-08	criteria provided, single submitter	clinical testing	This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 497 of the DDX3X protein (p.Ala497Val). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of DDX3X-related conditions (PMID: 32135084; Invitae). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 207818). 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: "Not Available"; Align-GVGD: "Class C55"). For these reasons, this variant has been classified as Pathogenic.
Revvity Omics, Revvity	RCV003144153	SCV003828818	likely pathogenic	Intellectual disability, X-linked 102	2022-06-08	criteria provided, single submitter	clinical testing
Lifecell International Pvt. Ltd	RCV003144153	SCV003922404	likely pathogenic	Intellectual disability, X-linked 102		criteria provided, single submitter	clinical testing	A Heterozygous Missense variant c.1490C>T in Exon 13 of the DDX3X gene that results in the amino acid substitution p.Ala497Val was identified. The observed variant is novel in gnomAD exomes and genomes, respectively. The severity of the impact of this variant on the protein is high, based on the effect of the protein and REVEL score. Rare Exome Variant Ensemble Learner (REVEL) is an ensembl method for predicting the pathogenicity of missense variants based on a combination of scores from 13 individual tools: MutPred, FATHMM v2.3, VEST 3.0, PolyPhen-2, SIFT, PROVEAN, MutationAssessor, MutationTaster, LRT, GERP++, SiPhy, phyloP, and phastCons. The REVEL score for an individual missense variant can range from 0 to 1, with higher scores reflecting greater likelihood that the variant is disease-causing. ClinVar has also classified this variant as Pathogenic [Variation ID: 207818]. The observed missense change has been previously observed in individual(s) with clinical features of DDX3X-related conditions (Lennox AL, et.al., 2020). For these reasons, this variant has been classified as Likely Pathogenic.
CeGaT Center for Human Genetics Tuebingen	RCV001857666	SCV005330406	pathogenic	not provided	2024-08-01	criteria provided, single submitter	clinical testing	DDX3X: PS2, PM1, PM2, PM5, PS4:Moderate, PP2