Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001966488 | SCV002252929 | likely pathogenic | Neu-Laxova syndrome 2 | 2024-12-02 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Glu326*) in the PSAT1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 45 amino acid(s) of the PSAT1 protein. This variant is present in population databases (rs199998249, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with PSAT1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1467660). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. This variant disrupts the C-terminus of the PSAT1 protein. Other variant(s) that disrupt this region (p.Arg342Aspfs*6) have been observed in individuals with PSAT1-related conditions (PMID: 25152457). This suggests that this may be a clinically significant region of the protein. 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. |