ClinVar Miner

Submissions for variant NM_000520.6(HEXA):c.1330+1G>A (rs767041069)

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
Counsyl RCV000410148 SCV000487086 pathogenic Tay-Sachs disease 2016-10-04 criteria provided, single submitter clinical testing
GeneDx RCV000438026 SCV000516070 pathogenic not provided 2015-03-19 criteria provided, single submitter clinical testing The c.1330+1 G>A splice site variant in the HEXA gene has previously been reported previously inassociation with infantile-onset Tay-Sachs disease in an individual who was homozygous for c.1330+1G>A (Montalvo et al., 2002). This variant destroys the canonical splice donor site in intron 11, and isexpected to cause abnormal gene splicing. Therefore, we interpret this variant as pathogenic.
Integrated Genetics/Laboratory Corporation of America RCV000410148 SCV001362842 pathogenic Tay-Sachs disease 2019-04-11 criteria provided, single submitter clinical testing Variant summary: HEXA c.1330+1G>A is located in a canonical splice-site and is predicted to affect mRNA splicing resulting in a significantly altered protein due to either exon skipping, shortening, or inclusion of intronic material. Several computational tools predict a significant impact on normal splicing: Three predict the variant abolishes a 5' splicing donor site. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 4.1e-06 in 245850 control chromosomes (gnomAD) and has been reported in the literature in individuals affected with Tay-Sachs Disease and Juvenile GM2 gangliosidosis (Montalvo_2005, Maegawa_2006, Zampieri_2012). These data indicate that the variant is likely to be associated with disease. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic. Based on the evidence outlined above, the variant was 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.