Arina Puzriakova commented on gene: TTN: The recent MOI update on this panel was done following an audit of genes with different MOIs on component panels of the same superpanel. These were reviewed by the curation team accounting for respective panel scope and final MOIs were validated by the Genomics England clinical team.
Arina Puzriakova Mode of inheritance for gene TTN was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Ellen McDonagh Added comment: Comment on list classification: Promoted from Red to Green due to overall the majority of reviews are Green, and there is a consensus that although classifying variants in this is difficult, additional phenotyping studies can aid in confirmation of diagnosis and that this gene should be included on this panel.
Chiara Marini Bettolo commented on gene: TTN: Disese spectrum can be very variable from congenital myopathy, cardiomyopathy, distal weakness, HMERF to LGMD. Known form of LGMD2J or LGMDR10
Louise Daugherty Phenotypes for gene: TTN were changed from Muscular dystrophy, limb-girdle, type 2J 608807 to Muscular dystrophy, limb-girdle, type 2J, 608807; Limb girdle muscular dystrophy; Distal myopathy; Myofibrillar myopathy; Congenital myopathy; dilated cardiomyopathy
Elizabeth Harris commented on gene: TTN: Currently only recurrent HMERF associated mutations are reported by this lab but truncating variants are also of great clinical interest. Difficulty classifying variants in titin should not be a reason not to include this gene as additional phenotyping studies such as muscle MRI, biopsy review and protein analysis is often extremely helpful in confirming or refuting the diagnosis.
Elizabeth Harris commented on gene: TTN: Loss of function variants are simpler to classify but missense variants are also reported as pathogenic. The analysis of titin variants is more complex than this proforma allows for
Elizabeth Harris reviewed gene: TTN: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: PMID: 28716623; Phenotypes: Limb girdle muscular dystrophy, congenital myopathy, myofibrillar myopathy; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes