ClinVar Miner

Submissions for variant NM_000520.6(HEXA):c.436del (p.Val146fs) (rs1057517174)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000411678 SCV000486867 likely pathogenic Tay-Sachs disease 2016-08-26 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000411678 SCV000917521 likely pathogenic Tay-Sachs disease 2018-11-19 criteria provided, single submitter clinical testing Variant summary: HEXA c.436delG (p.Val146PhefsX53) 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 (e.g. p.Gln390X, p.Tyr427fsX5, p.Arg510X). The variant was absent in 246232 control chromosomes (gnomAD). The variant, c.436delG, has been reported in the literature in a homozygous individual affected with Tay-Sachs Disease (Mules 1992). These data indicate that the variant may be associated with disease. 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 likely pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic.

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