ClinVar

Description

The AMH c.35T>G variant is predicted to result in the amino acid substitution p.Val12Gly. This variant has been reported in the compound heterozygous and homozygous states in two families with male individuals affected with persistent Mullerian duct syndrome (Imbeaud et al. 1994. PubMed ID: 8162013; Mazen et al. 2011. PubMed ID: 22188863). This variant has also been reported in the heterozygous state in female individuals with polycystic ovary syndrome (Gorsic et al. 2017. PubMed ID: 28505284). At PreventionGenetics, this variant was observed in the homozygous state in an individual with neurodevelopmental features, musculoskeletal features, dysmorphic features, gastrointestinal and genitourinary issues. Functional studies have conflicting results on the impact of this variant; a dual luciferase reporter assay showed significantly reduced AMH signaling (Gorsic et al. 2017. PubMed ID: 28505284), while another luciferase reporter assay showed comparable bioactivity to wildtype (Meng et al. 2023, PubMedID: 37004205). This variant is present in 0.35% of alleles in individuals of European (Non-Finnish) descent (as displayed in the table above). However, in gnomAD v4 (available only on GRCh38) 8 homozygotes are documented, which is higher than expected for this disorder. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.