ZNF674

Inheritance Pattern: XL

Disease ID:MONDO:0100284

Submitter: ClinGen

ZNF674 was first reported in relation to X-linked intellecutal disability in 2006 (Lugtenberg et al., PMID: 16385466). These authors identified three unique variants in the ZNF674 gene in three unrelated families with X-linked intellectual disability, including two missense variants and a stop-gained variant. However, there is insufficient evidence for the pathogenicity of these variants: one of the families with a missense variant also carried a translocation that co-segregated with the phenotype, the other missense variant was common in the general population, and stop-gained and other predicted null variants are also common in the general population, as noted by Piton et al. (2013) (PMID: 23871722). Delphin et al. (2012) also reported two patients with deletions encompassing the ZNF674 gene who did not have intellectual disability (PMID: 22126752). No experimental evidence linking variation in the ZNF674 gene to intellectual disability was identified. In summary, the evidence supporting the relationship between ZNF674 and X-linked intellectual disability has been disputed and no valid evidence remains to support the claim. More evidence is needed to either support or entirely refute the role ZNF674 plays in this disease. This classification was approved by the ClinGen Intellectual Disability and Autism Gene Curation Expert Panel on 5/4/2021.

Inheritance Pattern: XL

Disease ID:MONDO:0001071

Submitter: Ambry Genetics