ClinVar Miner

Submissions for variant NM_000520.6(HEXA):c.929_930del (p.Ser310fs) (rs751248523)

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
Mayo Clinic Laboratories, Mayo Clinic RCV000681660 SCV000809107 pathogenic Tay-Sachs disease 2018-06-27 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000681660 SCV001362844 pathogenic Tay-Sachs disease 2019-01-22 criteria provided, single submitter clinical testing Variant summary: HEXA c.929_930delCT (p.Ser310CysfsX13) 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 (eg. p.Gln390X, p.Tyr427fsX5, p.Arg510X). The variant allele was found at a frequency of 5.3e-05 in 246224 control chromosomes (gnomAD). This frequency is not significantly higher than expected for a pathogenic variant in HEXA causing Tay-Sachs Disease (5.3e-05 vs 0.0014), allowing no conclusion about variant significance. c.929_930delCT has been reported in the literature in individuals affected with Tay-Sachs Disease (Fernandes_1992, Nestrasil_2018, Utz_2015, Utz_2017). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. A ClinVar submission from a clinical diagnostic laboratory (evaluation after 2014) cites the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Invitae RCV000681660 SCV001588140 pathogenic Tay-Sachs disease 2020-02-06 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Ser310Cysfs*13) in the HEXA gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs751248523, ExAC 0.02%). This variant has been observed in individual(s) with Tay-Sachs disease (PMID: 1302612). Loss-of-function variants in HEXA are known to be pathogenic (PMID: 1833974, 8490625). For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV001566339 SCV001789841 pathogenic not provided 2019-10-28 no assertion criteria provided clinical testing Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at a significant frequency in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 1302612, 25557439)

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.