Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Department of Biochemistry, |
RCV001352914 | SCV001547516 | uncertain significance | Intellectual disability, X-linked syndromic, Turner type | 2021-03-25 | criteria provided, single submitter | research | Using whole-exome sequencing and Sanger sequencing we detected the variant NM_031407.5(HUWE1):c.12639G>A (p.Met4213Ile) in two males from unrelated families and different genetic backgrounds manifesting a phenotype reminiscent of Mental retardation, X-linked syndromic, Turner type. The variant was not detected in their mothers or siblings; however, we did not have paternal DNA. It was predicted pathogenic by several in silico tools and was absent in the gnomAD v2.1.1 database. This variant affected a conserved amino-acid in vertebrates inside the HECT domain of the protein. Although we believe this is a pathogenic variant, it fits the ACMG 2015 criteria for variants of uncertain significance. Functional evidence or identifying more patients (probably one independent patient) harboring this variant are necessary to determine its pathogenicity and increase its ACMG 2015 pathogenicity classification to pathogenic/likely pathogenic. |