ClinVar Miner

Submissions for variant NM_000521.4(HEXB):c.298C>T (p.Arg100Ter)

dbSNP: rs1007338250
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Foundation for Research in Genetics and Endocrinology, FRIGE's Institute of Human Genetics RCV000761558 SCV000889930 pathogenic Sandhoff disease 2019-03-12 criteria provided, single submitter clinical testing The R100X variant in the HEXB gene has been reported in 2 Indian patients with autosomal recessive Sandhoff disease (Tamhankar et al 2015) and is absent in the gnomAD database. Furthermore, nonsense mutations affecting HEXB gene is a known disease mechanism for Sandhoff disease and the R100X variant has been predicted to be pathogenic in silico by DANN, GERP, LRT and MutationTaster. In summary, the R100X variant meets the ACMG criteria to be classified as pathogenic based upon literature, absence from controls and computational evidence.
Baylor Genetics RCV000761558 SCV001162988 pathogenic Sandhoff disease criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000761558 SCV003525921 pathogenic Sandhoff disease 2022-02-25 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg100*) in the HEXB gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in HEXB are known to be pathogenic (PMID: 7550345, 18758829). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with Sandhoff disease (PMID: 26582265). ClinVar contains an entry for this variant (Variation ID: 623479). For these reasons, this variant has been classified as 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.