ClinVar Miner

Submissions for variant NM_000520.6(HEXA):c.78G>A (p.Trp26Ter)

dbSNP: rs121907964
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000004117 SCV000917514 pathogenic Tay-Sachs disease 2018-06-04 criteria provided, single submitter clinical testing Variant summary: HEXA c.78G>A (p.Trp26X) 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. c.1168C>T, p.Gln390X; c.1274_1277dupTATC, p.Tyr427fsX5). The variant was absent in 121186 control chromosomes. c.78G>A has been reported in the literature in individuals affected with Tay-Sachs Disease. These data indicate that the variant is likely to be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function. The most pronounced variant effect results in <10% of normal 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 pathogenic.
Invitae RCV000004117 SCV001586702 pathogenic Tay-Sachs disease 2022-10-31 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 3911). This premature translational stop signal has been observed in individual(s) with Tay-Sachs disease (PMID: 1833974, 21967858, 25606403). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Trp26*) 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).
OMIM RCV000004117 SCV000024283 affects Tay-Sachs disease 1993-01-01 no assertion criteria provided literature only
Natera, Inc. RCV000004117 SCV002089763 pathogenic Tay-Sachs disease 2017-03-17 no assertion criteria provided clinical testing

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