ClinVar Miner

Submissions for variant NM_000520.6(HEXA):c.1499del (p.Leu500fs) (rs1567295184)

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
Integrated Genetics/Laboratory Corporation of America RCV000758204 SCV000917516 likely pathogenic Tay-Sachs disease 2018-05-18 criteria provided, single submitter clinical testing Variant summary: HEXA c.1499delT (p.Leu500CysfsX9) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory (e.g., p.Arg510X and p.Leu517fsX7). The variant was absent in 121482 control chromosomes (ExAC and publications). The variant, c.1499delT, has been reported in the literature in two individuals: one compound heterozygote affected with adult-onset Tay-Sachs Disease (Barritt_2017) and one obligate carrier parent of an affected child (McGinniss_2002). Barritt_2017 reports enzyme activity levels in one patient of 10%-<30% of normal HexA activity. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic.
Sema4, Sema4 RCV000758204 SCV000886516 pathogenic Tay-Sachs disease 2018-10-26 no assertion criteria provided clinical testing
Natera Inc RCV000758204 SCV001190678 likely pathogenic Tay-Sachs disease 2019-05-20 no assertion criteria provided clinical testing

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.