ClinVar Miner

Submissions for variant NM_000521.4(HEXB):c.1642_1657del (p.Ala548fs)

dbSNP: rs1749847524
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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001206614 SCV001377930 likely pathogenic Sandhoff disease 2019-09-26 criteria provided, single submitter clinical testing This variant has been observed in an individual affected with Sandhoff disease (PMID: 30075786). This sequence change results in a premature translational stop signal in the HEXB gene (p.Ala548Metfs*23). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 9 amino acids of the HEXB protein. This variant is not present in population databases (ExAC no frequency). This variant disrupts a region of the protein in which other variants (p.Gly549Arg, p.Cys551Tyr) have been observed in individuals with HEXB-related conditions (PMID: 28281504, 24461908). This suggests that this may be a clinically significant region of the HEXB protein. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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