Submissions for variant NM_001374828.1(ARID1B):c.5635G>T (p.Glu1879Ter)

Minimum review status:		Collection method:
Minimum conflict level: Report conflict between different conditions
		ClinVar version:

Total submissions: 2

Download table as spreadsheet

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV001249783	SCV001423818	pathogenic	Coffin-Siris syndrome	2019-09-10	criteria provided, single submitter	clinical testing	The ARID1B c.5266G>T (p.Glu1756Ter) variant, also known as c.5386G>T (p.Glu1796Ter), is a stop-gained variant that is predicted to result in a premature truncation of the protein. A literature search was performed for the gene, cDNA change, and amino acid change. No publications were found based on this search. This variant is not found in the Genome Aggregation Database despite good sequencing coverage, so the variant is presumed to be rare. Based on the predicted truncating nature of the variant, its rarity, and identification in a de novo state, the ARID1B p.Glu1756Ter variant is classified as pathogenic for Coffin-Siris Syndrome.
Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard	RCV003225962	SCV003922232	likely pathogenic	Coffin-Siris syndrome 1	2023-05-02	criteria provided, single submitter	curation	The heterozygous p.Glu1756Ter variant in ARID1B was identified by our study in one individual with agenesis of the corpus callosum. Trio exome analysis showed this variant to be de novo. The p.Glu1756Ter variant in ARID1B has not been previously reported in individuals with Coffin-Siris syndrome 1. This variant has also been reported in ClinVar (Variation ID: 973330) and has been interpreted as pathogenic by Illumina. This variant was absent from large population studies. This nonsense variant leads to a premature termination codon at position 1756. This alteration occurs within the last exon and is more likely to escape nonsense mediated decay (NMD) and result in a truncated protein. Heterozygous loss of function of the ARID1B gene is an established disease mechanism in autosomal dominant Coffin-Siris syndrome 1. In summary, although additional studies are required to fully establish its clinical significance, this variant is likely pathogenic for autosomal dominant Coffin-Siris syndrome 1. ACMG/AMP Criteria applied: PVS1_Strong, PS2_Supporting, PM2_Supporting (Richards 2015).

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.