Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Illumina Laboratory Services, |
RCV004527803 | SCV000915833 | uncertain significance | DLL3-related disorder | 2018-10-10 | criteria provided, single submitter | clinical testing | The DLL3 c.602delG (p.Gly201ValfsTer40) variant results in a frameshift and is predicted to result in premature termination of the protein. The p.Gly201ValfsTer40 variant has been reported in one study in which it was found in a homozygous state in one individual with spondylocostal dysostoses (Turnpenny et al. 2003). Control data are unavailable for this variant and it is also not found in the 1000 Genomes Project, the Exome Sequencing Project, the Exome Aggregation Consortium or the Genome Aggregation Database. Based on the limited evidence and potential impact of frameshift variants, the p.Gly201ValfsTer40 variant has been classified as a variant of unknown significance but suspicious for pathogenicity for DLL3-related disorders. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. |
| Labcorp Genetics |
RCV001385889 | SCV001585903 | pathogenic | not provided | 2023-12-12 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Gly201Valfs*40) in the DLL3 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in DLL3 are known to be pathogenic (PMID: 12746394). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This premature translational stop signal has been observed in individual(s) with spondylocostal dysostosis (PMID: 12746394). ClinVar contains an entry for this variant (Variation ID: 632312). For these reasons, this variant has been classified as Pathogenic. |