Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV001772016 | SCV001992472 | uncertain significance | not provided | 2020-01-02 | criteria provided, single submitter | clinical testing | Not observed in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Identified in patients with Warburg-Cinotti syndrome in published literature (Xu et al., 2018); This variant is associated with the following publications: (PMID: 23637089, 30449416) |
| Illumina Laboratory Services, |
RCV000755661 | SCV004801588 | uncertain significance | Warburg-cinotti syndrome | 2019-09-13 | criteria provided, single submitter | clinical testing | The DDR2 c.2219A>G p.(Tyr740Cys) missense variant has been identified in four individuals from a single family with a phenotype consistent with Warburg-Cinotti syndrome. The variant was identified in a de novo state in the affected mother (Xu et al. 2018). This variant is not observed in version 2.1.1 of the Genome Aggregation Database. The Tyr740 residue is conserved across the family of tyrosine kinase receptors and located within the kinase activation loop where it is one of three tyrosine residues which upon phosphorylation regulate kinase catalytic activity and are critical for receptor activation (Borza et al. 2014). Patient fibroblasts harboring the p.Tyr740Cys variant show elevated levels of DDR2 phosphorylation when grown in serum starved media, suggesting that the variant has a gain of function mechanism resulting in ligand independent autophosphorylation and activation of the receptor (Xu et al. 2018). Based on the available evidence, the c.2219A>G p.(Tyr740Cys) variant is classified as a variant of uncertain significance for Warburg-Cinotti syndrome. |
| Center for Medical Genetics and Molecular Medicine, |
RCV000755661 | SCV000840082 | pathogenic | Warburg-cinotti syndrome | 2018-10-12 | no assertion criteria provided | clinical testing | Variant found in several individuals with acro-osteolysis, tendency to form keloind-like skin tumors, and corneal vascularization. |
| OMIM | RCV000755661 | SCV000883060 | pathogenic | Warburg-cinotti syndrome | 2019-02-13 | no assertion criteria provided | literature only |