Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Eurofins Ntd Llc |
RCV000723406 | SCV000330966 | pathogenic | not provided | 2016-07-05 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000390326 | SCV001362847 | pathogenic | Sandhoff disease | 2024-08-08 | criteria provided, single submitter | clinical testing | Variant summary: HEXB c.1023_1026delTGAG (p.Ser341ArgfsX30) 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. The variant allele was found at a frequency of 5.2e-05 in 251288 control chromosomes, predominantly at a frequency of 0.00038 within the Latino subpopulation in the gnomAD database. This frequency is not significantly higher than estimated for a pathogenic variant in HEXB causing Sandhoff Disease (5.2e-05 vs 0.0015), allowing no conclusion about variant significance. To our knowledge, no occurrence of c.1023_1026delTGAG in individuals affected with Sandhoff Disease and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 280975). Based on the evidence outlined above, the variant was classified as pathogenic. |
| Labcorp Genetics |
RCV000390326 | SCV001394593 | pathogenic | Sandhoff disease | 2024-11-28 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Ser341Argfs*30) 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 (rs776476415, gnomAD 0.04%). This variant has not been reported in the literature in individuals affected with HEXB-related conditions. ClinVar contains an entry for this variant (Variation ID: 280975). For these reasons, this variant has been classified as Pathogenic. |
| Fulgent Genetics, |
RCV000390326 | SCV002813379 | pathogenic | Sandhoff disease | 2024-02-05 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV000723406 | SCV003927494 | pathogenic | not provided | 2023-05-19 | criteria provided, single submitter | clinical testing | Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Has not been previously published as pathogenic or benign to our knowledge |
| Counsyl | RCV000390326 | SCV000792774 | likely pathogenic | Sandhoff disease | 2017-07-12 | no assertion criteria provided | clinical testing |