Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV004702587 | SCV005202362 | uncertain significance | not specified | 2024-07-31 | criteria provided, single submitter | clinical testing | Variant summary: SKIC2 c.1297C>T (p.Arg433Cys) results in a non-conservative amino acid change located in the DEAD/DEAH box helicase domain (IPR011545) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. Consensus agreement among computation tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 1.1e-05 in 1605784 control chromosomes. This frequency is not significantly higher than estimated for a pathogenic variant in SKIC2 causing Trichohepatoenteric Syndrome (1.1e-05 vs 0.00062), allowing no conclusion about variant significance. c.1297C>T has been reported in the literature in at-least one individual affected with Trichohepatoenteric Syndrome (example: Taher_2020). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 34414925, 33114497). ClinVar contains an entry for this variant (Variation ID: 828128). Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic. |
| Biochemical Molecular Genetic Laboratory, |
RCV001027997 | SCV001190757 | likely pathogenic | Trichohepatoenteric syndrome 2 | 2020-02-05 | no assertion criteria provided | clinical testing |