ClinVar Miner

Submissions for variant NM_139058.3(ARX):c.1444G>A (p.Gly482Ser) (rs1468724042)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Institute for Genomic Medicine (IGM) Clinical Laboratory,Nationwide Children's Hospital RCV001003472 SCV001161761 likely pathogenic Epileptic encephalopathy, early infantile, 1 2017-11-09 criteria provided, single submitter clinical testing [ACMG/AMP: PS2, PM2, PP2, PP3]; A de novo mosaic variant [PS2] within the ARX gene was detected and confirmed by sanger sequencing. This alteration results in the replacement of a glycine residue with a serine at amino acid 482 (p.Gly482Ser), and occurs at a position which is evolutionarily conserved and predicated to have a deleterious effect based on in silico modeling [PP3]. Notably, a single hemizygous allele with the p.Gly482Ser variant has been reported in the gnomAD population database among approximately 140,000 total alleles at that position [PM2]. The spectrum of disease associated variation within ARX is broad, and includes polyalanine expansion, truncating alterations, insertion deletion events and missense changes (PMID: 17668384; 20300201). Missense variants are a common mechanism of disease in this gene and the rate of benign missense variants is low [PP2]. Mosaicism has been previously documented in ARX (PMID: 16523516).

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