Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001194423 | SCV001363966 | likely pathogenic | Sandhoff disease | 2022-09-02 | criteria provided, single submitter | clinical testing | Variant summary: HEXB c.1345delT (p.Trp449GlyfsX3) 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 allele was found at a frequency of 4e-06 in 251416 control chromosomes (gnomAD). c.1345delT has been reported in the literature in an individual affected with Sandhoff Disease (example: Zhang_1994). This data do not allow any conclusion about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 and all classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| Invitae | RCV001194423 | SCV002167386 | pathogenic | Sandhoff disease | 2023-10-13 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Trp449Glyfs*3) 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). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This premature translational stop signal has been observed in individual(s) with Sandhoff disease (PMID: 8162015). This variant is also known as ΔT1344. ClinVar contains an entry for this variant (Variation ID: 929241). For these reasons, this variant has been classified as Pathogenic. |
| Fulgent Genetics, |
RCV001194423 | SCV002792164 | pathogenic | Sandhoff disease | 2021-09-09 | criteria provided, single submitter | clinical testing | |
| Natera, |
RCV001194423 | SCV002084946 | likely pathogenic | Sandhoff disease | 2020-12-21 | no assertion criteria provided | clinical testing |