Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Eurofins Ntd Llc |
RCV000723437 | SCV000331026 | pathogenic | not provided | 2016-09-07 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV000286253 | SCV001579760 | pathogenic | Sandhoff disease | 2024-01-07 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Arg170*) 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 (rs753823903, gnomAD 0.006%). This premature translational stop signal has been observed in individual(s) with Sandhoff disease (PMID: 22789865). ClinVar contains an entry for this variant (Variation ID: 281002). For these reasons, this variant has been classified as Pathogenic. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000286253 | SCV001774729 | likely pathogenic | Sandhoff disease | 2021-08-02 | criteria provided, single submitter | clinical testing | Variant summary: HEXB c.508C>T (p.Arg170X) 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 1.6e-05 in 251576 control chromosomes (gnomAD and publication data). c.508C>T has been reported in the literature in one individual affected with Sandhoff Disease (Gort_2012). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Three ClinVar submitters (evaluation after 2014) cite the variant as pathogenic (n=2) and likely pathogenic (n=1). Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| Counsyl | RCV000286253 | SCV000794209 | likely pathogenic | Sandhoff disease | 2017-09-19 | no assertion criteria provided | clinical testing |