TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29331	88216;88217;88218	chr2:178557271;178557270;178557269	chr2:179421998;179421997;179421996
N2AB	27690	83293;83294;83295	chr2:178557271;178557270;178557269	chr2:179421998;179421997;179421996
N2A	26763	80512;80513;80514	chr2:178557271;178557270;178557269	chr2:179421998;179421997;179421996
N2B	20266	61021;61022;61023	chr2:178557271;178557270;178557269	chr2:179421998;179421997;179421996
Novex-1	20391	61396;61397;61398	chr2:178557271;178557270;178557269	chr2:179421998;179421997;179421996
Novex-2	20458	61597;61598;61599	chr2:178557271;178557270;178557269	chr2:179421998;179421997;179421996
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: TTG
• RefSeq wild type template codon: AAC
• Domain: Fn3-101
• Domain position: 95
• Structural Position: 129
• Q(SASA): 0.2782
• Predicted PPI site: N

Reported SAVs

SNV	RS	DUET	PolyPhen-2	Condel	Rhapsody	REVEL	MVP	Source	MAF	Disease	Zygosity	Site annotation	mCSM PPI	Predicted PPI site	Comments	AFR	AMR	AMS	ASJ	EAS	EUR	FIN	MDE	NFE	SAS	OTH
L/M	None	None	0.999	N	0.682	0.157	0.429091045357	gnomAD-4.0.0	1.3684E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79884E-06	0	0

Saturation Mutagenesis

SAV	AlphaMissense (IC)	AlphaMissense Class (IC)	AlphaMissense (N2AB)	AlphaMissense Class (N2AB)	mCSM	mCSM class	PolyPhen-2	PolyPhen-2 Class	Rhapsody	Rhapsody Class	Condel	Condel Score	Site annotation	mCSM PPI	Predicted PPI site
L/A	0.6007	likely_pathogenic	0.582	pathogenic	-1.118	Destabilizing	0.998	D	0.783	deleterious	None	None	None	None	N
L/C	0.7699	likely_pathogenic	0.7626	pathogenic	-0.952	Destabilizing	1.0	D	0.81	deleterious	None	None	None	None	N
L/D	0.9665	likely_pathogenic	0.9581	pathogenic	-0.204	Destabilizing	1.0	D	0.834	deleterious	None	None	None	None	N
L/E	0.8267	likely_pathogenic	0.7961	pathogenic	-0.187	Destabilizing	0.999	D	0.846	deleterious	None	None	None	None	N
L/F	0.3592	ambiguous	0.3182	benign	-0.597	Destabilizing	0.999	D	0.721	deleterious	N	0.482960719	None	None	N
L/G	0.9126	likely_pathogenic	0.9088	pathogenic	-1.411	Destabilizing	0.999	D	0.841	deleterious	None	None	None	None	N
L/H	0.6669	likely_pathogenic	0.6322	pathogenic	-0.401	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
L/I	0.1746	likely_benign	0.1879	benign	-0.402	Destabilizing	0.998	D	0.655	prob.neutral	None	None	None	None	N
L/K	0.6698	likely_pathogenic	0.6481	pathogenic	-0.72	Destabilizing	0.999	D	0.841	deleterious	None	None	None	None	N
L/M	0.1915	likely_benign	0.1959	benign	-0.555	Destabilizing	0.999	D	0.682	prob.neutral	N	0.500103685	None	None	N
L/N	0.8413	likely_pathogenic	0.8158	pathogenic	-0.729	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
L/P	0.6324	likely_pathogenic	0.6488	pathogenic	-0.608	Destabilizing	1.0	D	0.824	deleterious	None	None	None	None	N
L/Q	0.5127	ambiguous	0.4841	ambiguous	-0.801	Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	N
L/R	0.5558	ambiguous	0.5365	ambiguous	-0.221	Destabilizing	0.999	D	0.853	deleterious	None	None	None	None	N
L/S	0.7895	likely_pathogenic	0.7559	pathogenic	-1.366	Destabilizing	0.999	D	0.84	deleterious	N	0.479824413	None	None	N
L/T	0.5569	ambiguous	0.548	ambiguous	-1.22	Destabilizing	0.999	D	0.809	deleterious	None	None	None	None	N
L/V	0.1749	likely_benign	0.1889	benign	-0.608	Destabilizing	0.997	D	0.738	deleterious	N	0.391069278	None	None	N
L/W	0.5838	likely_pathogenic	0.5798	pathogenic	-0.644	Destabilizing	1.0	D	0.731	deleterious	N	0.485279076	None	None	N
L/Y	0.6809	likely_pathogenic	0.6542	pathogenic	-0.414	Destabilizing	0.999	D	0.819	deleterious	None	None	None	None	N

Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.