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Incidentalome v1.10 TTN Sarah Milton changed review comment from: Summary of phenotypes as per Clingen:

Dilated cardiomyopathy 1G, MONDO:0011400
- Definitive association
- AD
- Molecular mechanism - truncating variants in exon with sufficiently high PSI, exact mechanism remains unclear - haploinsufficiency on it's own unlikely to be the only contributing factor, some papers postulate accumulation of truncated poison peptides contribute.

TTN-related myopathy, MONDO:0100175
- Definitive association
- AR
- Lumped: limb-girdle muscular dystrophy, (MIM #608807), centronuclear myopathy, Salih myopathy (MIM #611705), Emery-Dreifuss-like muscular dystrophy (not an OMIM entity), titinopathy with congenital contractures (not an OMIM entity), minicore myopathy (not an OMIM entity), distal titinopathy
- Presumably loss of function molecular mechanism, frameshift, deletion, missense, splice site variants have been called LP/P for this phenotype, PSI less relevant

Myopathy, myofibrillar, 9, with early respiratory failure MONDO:0011362
- Definitive association
- AD
- Missense variants in exon 344 A band

Tibial muscular dystrophy, MONDO:0010870
- Moderate association
- AD
- Variants in M line – missense and truncating exon 363

TTN-related myopathy, dominant-negative TTNsv, MONDO:1060225
- Moderate association
- AD
- Multiexon in frame deletion/CNV escape NMD, expressed
- Located in Z disk, A,I or A/M band deletions
- Phenotype ranges from arthrogryposis to adult onset distal myopathy

Hypertrophic cardiomyopathy, MONDO:0005045, AD
- Limited association
- AD

Arrhythmogenic right ventricular cardiomyopathy, MONDO:0016587
- Disputed association
- AD; to: Summary of phenotypes as per Clingen:

Dilated cardiomyopathy 1G, MONDO:0011400
- Definitive association
- AD
- Molecular mechanism - truncating variants in exon with sufficiently high PSI, exact mechanism remains unclear - haploinsufficiency on it's own unlikely to be the only contributing factor, some papers postulate accumulation of truncated poison peptides contribute.


TTN-related myopathy, MONDO:0100175
- Definitive association
- AR
- Lumped: limb-girdle muscular dystrophy, (MIM #608807), centronuclear myopathy, Salih myopathy (MIM #611705), Emery-Dreifuss-like muscular dystrophy (not an OMIM entity), titinopathy with congenital contractures (not an OMIM entity), minicore myopathy (not an OMIM entity), distal titinopathy
- Presumably loss of function molecular mechanism, frameshift, deletion, missense, splice site variants have been called LP/P for this phenotype, PSI less relevant


Myopathy, myofibrillar, 9, with early respiratory failure MONDO:0011362
- Definitive association
- AD
- Missense variants in exon 344 A band

Tibial muscular dystrophy, MONDO:0010870
- Moderate association
- AD
- Variants in M line – missense and truncating exon 363


TTN-related myopathy, dominant-negative TTNsv, MONDO:1060225
- Moderate association
- AD
- Multiexon in frame deletion/CNV escape NMD, expressed
- Located in Z disk, A,I or A/M band deletions
- Phenotype ranges from arthrogryposis to adult onset distal myopathy


Hypertrophic cardiomyopathy, MONDO:0005045, AD
- Limited association
- AD


Arrhythmogenic right ventricular cardiomyopathy, MONDO:0016587
- Disputed association
- AD
Incidentalome v1.0 FUS Gene migrated from ENSG00000089280 to ENSG00000089280 (gene set migration)
Incidentalome v0.273 FUS Bryony Thompson Marked gene: FUS as ready
Incidentalome v0.273 FUS Bryony Thompson Gene: fus has been classified as Green List (High Evidence).
Incidentalome v0.273 FUS Bryony Thompson Tag adult onset neurodegenerative tag was added to gene: FUS.
Incidentalome v0.273 FUS Bryony Thompson Phenotypes for gene: FUS were changed from to Amyotrophic lateral sclerosis 6, with or without frontotemporal dementia, MIM# 608030
Incidentalome v0.272 FUS Bryony Thompson Publications for gene: FUS were set to
Incidentalome v0.271 FUS Bryony Thompson Mode of inheritance for gene: FUS was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Incidentalome v0.145 TMEM43 Zornitza Stark Phenotypes for gene: TMEM43 were changed from to Arrhythmogenic right ventricular dysplasia 5, MIM# 604400; Auditory neuropathy, autosomal dominant 3, MIM# 619832; Emery-Dreifuss muscular dystrophy 7 (MIM#614302)
Incidentalome v0.142 TMEM43 Zornitza Stark edited their review of gene: TMEM43: Added comment: Association with deafness: MODERATE, two multiplex families with missense variants.

Association with muscular dystrophy LIMITED to MODERATE:
PMID: 21391237 (2011): Different variants reported in 2 adults with EDMD-related myopathy. Ile91Val present in gnomad, 20 hets. Other variant, Glu85Lys, presented in gnomad (1 het)

PMID: 30311943 (2019): 1 EDMD family reported with the same Glu85Lys variant. Muscle disease suspected at age of 17 in one family member.; Changed publications: 18313022, 21214875, 23812740, 22725725, 24598986, 29980933, 34050020, 21391237, 30311943; Changed phenotypes: Arrhythmogenic right ventricular dysplasia 5, MIM# 604400, Auditory neuropathy, autosomal dominant 3, MIM# 619832, Emery-Dreifuss muscular dystrophy 7 (MIM#614302)
Incidentalome v0.136 LMNA Zornitza Stark Phenotypes for gene: LMNA were changed from to Cardiomyopathy, dilated, 1A, MIM# 115200; Arrhythmogenic right ventricular cardiomyopathy; Lipodystrophy, familial partial, type 2, MIM# 151660; Emery-Dreifuss muscular dystrophy 2, MIM#181350; Mandibuloacral dysplasia 248370; Restrictive dermopathy, lethal 275210; Hutchinson-Gilford progeria 176670; Muscular dystrophy, congenital 613205
Incidentalome v0.132 LMNA Zornitza Stark edited their review of gene: LMNA: Changed rating: GREEN; Changed phenotypes: Cardiomyopathy, dilated, 1A, MIM# 115200, Arrhythmogenic right ventricular cardiomyopathy, Lipodystrophy, familial partial, type 2, MIM# 151660, Emery-Dreifuss muscular dystrophy 2, MIM#181350, Mandibuloacral dysplasia 248370, Restrictive dermopathy, lethal 275210, Hutchinson-Gilford progeria 176670, Muscular dystrophy, congenital 613205
Incidentalome v0.58 THSD4 Zornitza Stark gene: THSD4 was added
gene: THSD4 was added to Incidentalome. Sources: Literature
Mode of inheritance for gene: THSD4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: THSD4 were set to 32855533
Phenotypes for gene: THSD4 were set to Thoracic aortic aneurysm and dissection (TAAD)
Review for gene: THSD4 was set to GREEN
Added comment: 5 functional heterozygous variants in THSD4 (two lead to a premature termination codon) found in 5 families with TAAD. Variants segregated with disease in other family members. THSD4 encodes ADAMTSL6, a microfibril-associated protein that promotes fibrillin-1 matrix assembly. The THSD4 variants studied lead to haploinsufficiency or impaired assembly of fibrillin-1 microfibrils. Thsd4+/- mice showed progressive dilation of the thoracic aorta. Histologic examination of aortic samples from a patient carrying a THSD4 variant and from Thsd4+/- mice, revealed typical medial degeneration and diffuse disruption of extracellular matrix.
Sources: Literature
Incidentalome v0.0 FUS Zornitza Stark gene: FUS was added
gene: FUS was added to Incidentalome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: FUS was set to Unknown