Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Seattle Children's Hospital Molecular Genetics Laboratory, |
RCV001263535 | SCV005326356 | pathogenic | Visceral myopathy 1 | criteria provided, single submitter | clinical testing | The p.Glu196Asp variant substitutes the glycine at amino acid position 196 with an aspartic acid in the lateral bonding loop in subdomain 4 and is predicted to disrupt the salt bridge formed with p.Arg257 that is found in the wildtype ACTG2 protein (PMID: 33294969). The p.Glu196Asp variant has been reported in several unrelated individuals with pediatric intestinal pseudo-obstruction (PMID: 33294969, PMID: 33656779, PMID: 32810037, PMID: 33880338). Clinical findings reported in individuals with this variant include megacystis, abdominal distension, constipation, nausea and vomiting (Matera et al., 2021, Martire et al., 2021; Wei et al., 2021; Xiong et al., 2021). For the three cases where parents were tested, the variant was found to be a de novo change. Cultured smooth muscle cells derived from an individual with the the p.Glu196Asp variant showed decreased a smooth muscle actin protein levels and increased PDGFRA expression compared to controls, suggesting this variant impacts smooth muscle cell differentiation (PMID: 33656779). | |
| UOSD Genetics and Genomics of Rare Diseases, |
RCV001263535 | SCV001422493 | likely pathogenic | Visceral myopathy 1 | 2020-04-28 | no assertion criteria provided | provider interpretation |