Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| ARUP Laboratories, |
RCV001384264 | SCV007332900 | pathogenic | Marinesco-Sjögren syndrome | criteria provided, single submitter | clinical testing | The SIL1 c.1117del; p.Leu373CysfsTer33 variant is reported in the literature in multiple individuals affected with Marinesco-Sjogren syndrome (Ezgu 2014). This variant is found in the general population with an overall allele frequency of 0.000004 (1/250,422 alleles) in the Genome Aggregation Database (v2.1.1). This variant results in a premature termination codon in the last exon of the SIL1 gene. While this may not lead to nonsense-mediated decay, it is expected to create a truncated protein that would include a sequence of 33 amino acid residues not usually present. Based on available information, this variant is considered to be pathogenic. Ezgu F et al. Phenotype-genotype correlations in patients with Marinesco-Sjögren syndrome. Clin Genet. 2014 Jul;86(1):74-84. PMID: 23829326 | |
| Labcorp Genetics |
RCV001384264 | SCV001583693 | pathogenic | Marinesco-Sjögren syndrome | 2025-10-27 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Leu373Cysfs*33) in the SIL1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 89 amino acid(s) of the SIL1 protein. This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with Marinesco-Sjogren syndrome (PMID: 23829326). This variant is also known as c.1116delC. ClinVar contains an entry for this variant (Variation ID: 1071735). This variant disrupts a region of the SIL1 protein in which other variant(s) (p.Gln414*) have been determined to be pathogenic (PMID: 19471582). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. |