Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000810236 | SCV000950429 | likely pathogenic | Adenylosuccinate lyase deficiency | 2023-07-19 | criteria provided, single submitter | clinical testing | Disruption of this splice site has been observed in individual(s) with ADSL-related conditions (PMID: 31440721). 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 654306). This variant is present in population databases (rs761551284, gnomAD 0.0009%). This sequence change affects a donor splice site in intron 3 of the ADSL gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in ADSL are known to be pathogenic (PMID: 10888601, 20177786). |
| Gene |
RCV003329344 | SCV004036359 | likely pathogenic | not provided | 2023-03-24 | criteria provided, single submitter | clinical testing | Identified in a cohort with childhood epilepsy, but familial segregation information and additional clinical information was not included (Truty et al., 2019); Canonical splice site variant expected to result in aberrant splicing, although in the absence of functional evidence the actual effect of this sequence change is unknown.; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 31440721) |