ClinVar Miner

Submissions for variant NM_031407.7(HUWE1):c.12619G>A (p.Val4207Ile)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 1
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV003324242 SCV004029738 likely pathogenic Intellectual disability, X-linked syndromic, Turner type 2023-07-30 criteria provided, single submitter clinical testing Variant summary: HUWE1 c.12619G>A (p.Val4207Ile) results in a conservative amino acid change located in the HECT domain (IPR000569) of the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant was absent in 183367 control chromosomes. To our knowledge, no occurrence of c.12619G>A in individuals affected with Intellectual Disability, X-Linked Syndromic, Turner Type and no experimental evidence demonstrating its impact on protein function have been reported. However, this variant was observed as a de-novo occurrence in at-least one female proband with features of HUWE1-related disorder by exome analysis performed at our laboratory. De-novo variants in the HECT domain of HUWE1 have been reported in individuals with X-linked disability supporting a critical role of this region in protein function (PMID: 29180823). No submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.