ClinVar Miner

Submissions for variant NM_000489.6(ATRX):c.4825C>T (p.His1609Tyr)

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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 Human Genetics and Genomic Medicine, Uniklinik RWTH Aachen RCV003397224 SCV004102752 likely pathogenic Alpha thalassemia-X-linked intellectual disability syndrome 2023-11-02 criteria provided, single submitter clinical testing The variant has not been detected in the general population (gnomAD). It has not yet been described in the literature or in the ClinVar and dbSNP151 databases. Another amino acid substitution at this position (NM_000489.6:c.4826A>G, p.(His1609Arg)) has already been reported in a patient with ATRX syndrome (PMID: 7697714, PMID: 18409179) and is listed twice in ClinVar as (likely) pathogenic (Variation ID 11721). The variant is located in a mutational hotspot in the Snf2 domain and a destabilizing effect on the ATRX protein has been demonstrated for mutations of the highly conserved amino acid His1609. (PMID: 21505078) Bioinformatically, the change is classified as "probably disease-causing" (PolyPhen2, mutation taster, SIFT; CADDphred 27.8). The variant is currently considered as likely pathogenic (ACMG criteria).

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