Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000372047 | SCV000329863 | pathogenic | not provided | 2017-08-17 | criteria provided, single submitter | clinical testing | The Y184X nonsense variant in the HEXB gene has been reported previously in association with Sandhoff Disease (Sobek et al., 2013; Gaignard et al., 2013). This pathogenic variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. |
| Invitae | RCV000666419 | SCV001230648 | pathogenic | Sandhoff disease | 2022-11-01 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 280067). This premature translational stop signal has been observed in individual(s) with Sandhoff disease (PMID: 23046579). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Tyr184*) in the HEXB gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in HEXB are known to be pathogenic (PMID: 7550345, 18758829). |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000666419 | SCV001983503 | pathogenic | Sandhoff disease | 2021-09-12 | criteria provided, single submitter | clinical testing | Variant summary: HEXB c.552T>G (p.Tyr184X) 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. The variant was absent in 246712 control chromosomes. c.552T>G has been reported in the literature in individuals affected with Sandhoff Disease (example, Sobek_2012, Gaignard_2013, Mahdieh_2018). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
| Fulgent Genetics, |
RCV000666419 | SCV002800130 | pathogenic | Sandhoff disease | 2022-03-22 | criteria provided, single submitter | clinical testing | |
| Counsyl | RCV000666419 | SCV000790707 | likely pathogenic | Sandhoff disease | 2017-04-05 | no assertion criteria provided | clinical testing |