Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000674291 | SCV000799601 | likely pathogenic | Tay-Sachs disease | 2018-04-30 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV000674291 | SCV004297647 | likely pathogenic | Tay-Sachs disease | 2024-01-21 | criteria provided, single submitter | clinical testing | This sequence change falls in intron 4 of the HEXA gene. It does not directly change the encoded amino acid sequence of the HEXA protein. RNA analysis indicates that this variant induces altered splicing and may result in an absent or disrupted protein product. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individual(s) with Tay-Sachs disease (PMID: 9090529). It has also been observed to segregate with disease in related individuals. This variant is also known as +3tIVS4. ClinVar contains an entry for this variant (Variation ID: 558071). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Studies have shown that this variant results in skipping of exon 4 and introduces a premature termination codon (PMID: 9090529). The resulting mRNA is expected to undergo nonsense-mediated decay. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |