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| Fetal anomalies v1.185 | TNNT3 |
Rhiannon Mellis gene: TNNT3 was added gene: TNNT3 was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: TNNT3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: TNNT3 were set to 32779773 Phenotypes for gene: TNNT3 were set to Arthrogryposis, distal, type 2B2 Mode of pathogenicity for gene: TNNT3 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments Review for gene: TNNT3 was set to GREEN Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene. Additional comment: Clearly documented phenotype of distal arthrogryposis. Also, recent paper in Prenatal Diagnosis reporting a het pathogenic variant in TNNT3 in a fetus with FADS; that variant has previously only been described in a family with much milder distal arthrogryposis phenotype. PMID: 32779773 (copied from OMIM): In in vitro studies, Robinson et al. (2007) demonstrated that the TNNI2 R174Q (191043.0001) and R156X (191043.0002) mutations and the TNNT3 mutation R63H (600692.0001) resulted in a gain of function with increased ATPase activity in actin-activated myosin ATPase assays, reflecting increased calcium sensitivity and consistent with increased contractility. In patients, Robinson et al. (2007) concluded that the mutation would cause increased tension in developing muscles, thus resulting in contractures and limb deformities via an active process rather than a passive process. These findings implicated disturbed muscle function as the pathogenic mechanism underlying DA2B. Sources: Literature |
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| Fetal anomalies v0.134 | TNNI2 | Rebecca Foulger edited their review of gene: TNNI2: Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in March 2019. Clinical review and curation was performed by Lyn Chitty, Anna de Burca, Rhiannon Mellis, Richard Scott, Ellen McDonagh and Rebecca Foulger. Outcome of review: Confirmed that phenotype is fetally-relevant: keep on the Fetal anomalies panel as a Green gene.; Changed rating: GREEN | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.9 | TNNI2 | Rebecca Foulger reviewed gene: TNNI2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1 | TNNI2 |
Rebecca Foulger gene: TNNI2 was added gene: TNNI2 was added to Fetal anomalies. Sources: Expert Review Green,PAGE Additional Gene List Mode of inheritance for gene: TNNI2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Phenotypes for gene: TNNI2 were set to Arthrogryposis multiplex congenita, distal, type 2B 601680 |
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