Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| New York Genome Center | RCV001291683 | SCV001480264 | uncertain significance | Intellectual disability, autosomal dominant 41 | 2019-09-26 | criteria provided, single submitter | clinical testing | The c.40A>G (p.Arg14Gly) variant identified in the TBL1XR1 gene subsitutes a completely conserved Arginine for Glycine at amino acid 14/515 (coding exon 3/16). This variant is absent from gnomAD and ExAC, suggesting it is not a common benign variant in the populations represented in these databases. In silico algorithms predict this variant is Deleterious (Provean; Score: -6.30) and Damaging (SIFT; score: 0.001) to the function of the canonical transcript. This variant is absent from ClinVar and to our current knowledge has never been reported in affected individuals in the litearature. The p.Arg14 residue is within the N-terminal LisH domain of the protein which is important for oligomerization and transcriptional repression, however to date the few reported pathogenic TBL1XR1 variants were outside of this domain. Given the lack of compelling evidence supporting its pathogenicity, the c.40A>G (p.Arg14Gly) variant identified in the TBL1XR1 gene it is reported here as a Variant of Uncertain Significance. |
| New York Genome Center | RCV001291684 | SCV001480265 | uncertain significance | Pierpont syndrome | 2019-09-26 | criteria provided, single submitter | clinical testing | The c.40A>G (p.Arg14Gly) variant identified in the TBL1XR1 gene subsitutes a completely conserved Arginine for Glycine at amino acid 14/515 (coding exon 3/16). This variant is absent from gnomAD and ExAC, suggesting it is not a common benign variant in the populations represented in these databases. In silico algorithms predict this variant is Deleterious (Provean; Score: -6.30) and Damaging (SIFT; score: 0.001) to the function of the canonical transcript. This variant is absent from ClinVar and to our current knowledge has never been reported in affected individuals in the litearature. The p.Arg14 residue is within the N-terminal LisH domain of the protein which is important for oligomerization and transcriptional repression, however to date the few reported pathogenic TBL1XR1 variants were outside of this domain. Given the lack of compelling evidence supporting its pathogenicity, the c.40A>G (p.Arg14Gly) variant identified in the TBL1XR1 gene it is reported here as a Variant of Uncertain Significance. |
| Center for Genomic Medicine, |
RCV001291683 | SCV004809741 | uncertain significance | Intellectual disability, autosomal dominant 41 | 2024-04-04 | criteria provided, single submitter | clinical testing |