Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000630481 | SCV000751441 | likely pathogenic | Cystinuria | 2017-11-28 | criteria provided, single submitter | clinical testing | This variant is a gross deletion of the genomic region encompassing exons 2-10 of the SLC3A1 gene. The 5' boundary is likely confined to intron 1. The 3' end of this event is unknown as it extends through the termination codon beyond the assayed region for this gene and encompasses exons 2-14 of the PREPL gene. While this deletion is not anticipated to result in nonsense mediated decay, it is expected to create a truncated protein product or disrupt mRNA translation. Deletion of SLC3A1 exons 2-10 and PREPL exons 2-14 has not been reported in the literature in individuals with PREPL-related disease. However, a deletion which includes this region of the PREPL gene and all of the SLC3A1 gene has been reported in individuals with hypotonia–cystinuria syndrome (PMID: 22796000). Additionally, a smaller deletion encompassing exons 9-14 of the PREPL gene and exons 5-10 of the SLC3A1 gene has been reported in an individual affected with hypotonia-cystinuria syndrome (PMID: 24610330). 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. |
| Labcorp Genetics |
RCV001390053 | SCV001591640 | pathogenic | Myasthenic syndrome, congenital, 22 | 2020-10-06 | criteria provided, single submitter | clinical testing | This variant is a gross deletion of the genomic region encompassing exons 2-14 of the PREPL gene. The 5' boundary is likely confined to intron 1. If SLC3A1 has been tested and no copy number events are reported for it, then the 3' boundary of this event lies between the PREPL and SLC3A1 genes. If SLC3A1 has not been tested, the 3' end of this event is unknown as it extends beyond the assayed region of this test and may encompass additional genes including the SLC3A1 gene. This is expected to result in an absent or disrupted protein product. Isolated deletions of exons 2-14 of PREPL have not been reported in the literature. However, larger copy number events that include this region have been reported in individuals affected with hypotonia-cystinuria syndrome (PMID: 24610330, 22796000, 24610330). For these reasons, this variant has been classified as Pathogenic. |