ClinVar Miner

Submissions for variant NM_000520.6(HEXA):c.425_426del (p.Thr141_Phe142insTer)

dbSNP: rs1057519458
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000004138 SCV001581385 pathogenic Tay-Sachs disease 2022-10-13 criteria provided, single submitter clinical testing This variant is also known as frameshift codon 142. For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 3932). This premature translational stop signal has been observed in individual(s) with Tay-Sachs disease (PMID: 8490625). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Phe142*) in the HEXA gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in HEXA are known to be pathogenic (PMID: 1833974, 8490625).
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000004138 SCV001983501 pathogenic Tay-Sachs disease 2021-09-26 criteria provided, single submitter clinical testing Variant summary: HEXA c.425_426delTT (p.Phe142X) 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. The variant was absent in 251452 control chromosomes. c.425_426delTT has been reported in the literature in individuals affected with Tay-Sachs Disease and has been subsequently cited by others (example Akli_1993). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
OMIM RCV000004138 SCV000024304 affects Tay-Sachs disease 1993-01-01 no assertion criteria provided literature only
Natera, Inc. RCV000004138 SCV002089749 pathogenic Tay-Sachs disease 2017-03-16 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.