ClinVar Miner

Submissions for variant NM_000520.5(HEXA):c.1168C>T (p.Gln390Ter) (rs988192535)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000666873 SCV000791237 likely pathogenic Tay-Sachs disease 2017-05-05 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000666873 SCV000917515 pathogenic Tay-Sachs disease 2018-05-03 criteria provided, single submitter clinical testing Variant summary: HEXA c.1168C>T (p.Gln390X) 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.1274_1277dupTATC (p.Tyr427fsX5) and c.1528C>T (p.Arg510X)). The variant, c.1168C>T, has been reported in the literature in an individual affected with Tay-Sachs Disease presenting with no hexosaminidase A activity (Jin_2004). This data indicates that the variant may be associated with disease. 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 RCV000666873 SCV000939243 pathogenic Tay-Sachs disease 2018-08-27 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln390*) in the HEXA gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed as heterozygous in an unaffected individual (PMID: 9150157). Loss-of-function variants in HEXA are known to be pathogenic (PMID: 1833974, 8490625). For these reasons, this variant has been classified as Pathogenic.

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