TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3834	11725;11726;11727	chr2:178741733;178741732;178741731	chr2:179606460;179606459;179606458
N2AB	3517	10774;10775;10776	chr2:178741733;178741732;178741731	chr2:179606460;179606459;179606458
N2A	None	None	chr2:None	chr2:None
N2B	3471	10636;10637;10638	chr2:178741733;178741732;178741731	chr2:179606460;179606459;179606458
Novex-1	3596	11011;11012;11013	chr2:178741733;178741732;178741731	chr2:179606460;179606459;179606458
Novex-2	3663	11212;11213;11214	chr2:178741733;178741732;178741731	chr2:179606460;179606459;179606458
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGG
• RefSeq wild type template codon: CCC
• Domain: Ig-27
• Domain position: 15
• Structural Position: 24
• Q(SASA): 0.3465
• 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
G/R	rs749170112	-0.614	0.978	D	0.819	0.575	None	gnomAD-2.1.1	8.05E-06	None	None	None	None	N	None	0	5.8E-05	None	0	0	None	0	None	0	0	0
G/R	rs749170112	-0.614	0.978	D	0.819	0.575	None	gnomAD-4.0.0	3.18305E-06	None	None	None	None	N	None	0	4.57519E-05	None	0	0	None	0	0	0	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
G/A	0.3425	ambiguous	0.271	benign	-0.331	Destabilizing	0.926	D	0.707	prob.neutral	D	0.711780872	None	None	N
G/C	0.5311	ambiguous	0.4262	ambiguous	-0.851	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
G/D	0.3294	likely_benign	0.2526	benign	-0.22	Destabilizing	0.983	D	0.809	deleterious	None	None	None	None	N
G/E	0.3143	likely_benign	0.2477	benign	-0.365	Destabilizing	0.293	N	0.611	neutral	D	0.672348552	None	None	N
G/F	0.8685	likely_pathogenic	0.798	pathogenic	-0.955	Destabilizing	1.0	D	0.83	deleterious	None	None	None	None	N
G/H	0.7103	likely_pathogenic	0.6034	pathogenic	-0.61	Destabilizing	0.999	D	0.822	deleterious	None	None	None	None	N
G/I	0.8305	likely_pathogenic	0.7076	pathogenic	-0.37	Destabilizing	0.999	D	0.828	deleterious	None	None	None	None	N
G/K	0.6085	likely_pathogenic	0.51	ambiguous	-0.706	Destabilizing	0.983	D	0.807	deleterious	None	None	None	None	N
G/L	0.7854	likely_pathogenic	0.6911	pathogenic	-0.37	Destabilizing	0.991	D	0.802	deleterious	None	None	None	None	N
G/M	0.803	likely_pathogenic	0.7094	pathogenic	-0.397	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
G/N	0.4506	ambiguous	0.3724	ambiguous	-0.356	Destabilizing	0.991	D	0.815	deleterious	None	None	None	None	N
G/P	0.9735	likely_pathogenic	0.9522	pathogenic	-0.321	Destabilizing	0.996	D	0.815	deleterious	None	None	None	None	N
G/Q	0.5317	ambiguous	0.4419	ambiguous	-0.607	Destabilizing	0.983	D	0.816	deleterious	None	None	None	None	N
G/R	0.4736	ambiguous	0.3786	ambiguous	-0.337	Destabilizing	0.978	D	0.819	deleterious	D	0.703178336	None	None	N
G/S	0.2234	likely_benign	0.1772	benign	-0.598	Destabilizing	0.983	D	0.808	deleterious	None	None	None	None	N
G/T	0.5072	ambiguous	0.3817	ambiguous	-0.66	Destabilizing	0.991	D	0.801	deleterious	None	None	None	None	N
G/V	0.6856	likely_pathogenic	0.5321	ambiguous	-0.321	Destabilizing	0.989	D	0.807	deleterious	D	0.732688702	None	None	N
G/W	0.6506	likely_pathogenic	0.5459	ambiguous	-1.121	Destabilizing	1.0	D	0.797	deleterious	D	0.80328825	None	None	N
G/Y	0.7362	likely_pathogenic	0.6372	pathogenic	-0.755	Destabilizing	1.0	D	0.83	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.