ClinVar Miner

Submissions for variant NM_000520.6(HEXA):c.233G>A (p.Trp78Ter) (rs769035623)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000520763 SCV000622059 pathogenic not provided 2017-11-02 criteria provided, single submitter clinical testing The W78X variant in the HEXA gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The W78X variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016). We interpret W78X as a pathogenic variant.
Invitae RCV000984274 SCV001222985 pathogenic Tay-Sachs disease 2020-01-03 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Trp78*) in the HEXA gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs769035623, ExAC 0.002%). This variant has not been reported in the literature in individuals with HEXA-related disease. ClinVar contains an entry for this variant (Variation ID: 453185). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. Loss-of-function variants in HEXA are known to be pathogenic (PMID: 1833974, 8490625). For these reasons, this variant has been classified as Pathogenic.
Counsyl RCV000984274 SCV001132416 likely pathogenic Tay-Sachs disease 2019-01-24 no assertion criteria provided clinical testing

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