Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV004766913 | SCV005381078 | pathogenic | Sandhoff disease | 2024-08-14 | criteria provided, single submitter | clinical testing | Variant summary: The variant involves the deletion of exons 1-5 in the HEXB gene. A presumed nomenclature of c.(?_-29)_(669+1_670-1)del has been designated for the purposes of this classification. The exact breakpoint at the 5' end of this variant is unknown, therefore this deletion may extend upstream of the annotated region of this gene. Although the exact breakpoints of this deletion are not known, it is predicted to remove the initiation codon and result in an absence of protein or a truncation of the encoded protein due to translation initiation at a downstream site. The variant allele was found at a frequency of 9.2e-05 in 21694 control chromosomes. c.(?_-29)_(669+1_670-1)del has been reported in the literature in at least one compound heterozygous individual affected with Sandhoff Disease (e.g. Chardon_2015, Zanetti_2020). These data suggests that this variant is likely associated with Sandhoff Disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 26769462, 32036093). ClinVar contains an entry for this variant (Variation ID: 527972, 644276, 583659). Based on the evidence outlined above, the variant was classified as pathogenic. |