TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21786	65581;65582;65583	chr2:178583826;178583825;178583824	chr2:179448553;179448552;179448551
N2AB	20145	60658;60659;60660	chr2:178583826;178583825;178583824	chr2:179448553;179448552;179448551
N2A	19218	57877;57878;57879	chr2:178583826;178583825;178583824	chr2:179448553;179448552;179448551
N2B	12721	38386;38387;38388	chr2:178583826;178583825;178583824	chr2:179448553;179448552;179448551
Novex-1	12846	38761;38762;38763	chr2:178583826;178583825;178583824	chr2:179448553;179448552;179448551
Novex-2	12913	38962;38963;38964	chr2:178583826;178583825;178583824	chr2:179448553;179448552;179448551
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGC
• RefSeq wild type template codon: CCG
• Domain: Fn3-46
• Domain position: 30
• Structural Position: 32
• Q(SASA): 0.5299
• Predicted PPI site: I

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/C	None	None	1.0	D	0.805	0.516	0.784326782449	gnomAD-4.0.0	6.86059E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	9.00945E-07	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	0.7485	likely_pathogenic	0.7238	pathogenic	-0.281	Destabilizing	1.0	D	0.659	neutral	N	0.486402529	None	None	I
G/C	0.8071	likely_pathogenic	0.8055	pathogenic	-0.963	Destabilizing	1.0	D	0.805	deleterious	D	0.527361206	None	None	I
G/D	0.9067	likely_pathogenic	0.9091	pathogenic	-0.477	Destabilizing	1.0	D	0.743	deleterious	N	0.498203361	None	None	I
G/E	0.9403	likely_pathogenic	0.9455	pathogenic	-0.623	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	I
G/F	0.9631	likely_pathogenic	0.9614	pathogenic	-1.008	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	I
G/H	0.9476	likely_pathogenic	0.9485	pathogenic	-0.345	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	I
G/I	0.9407	likely_pathogenic	0.9366	pathogenic	-0.538	Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	I
G/K	0.953	likely_pathogenic	0.9607	pathogenic	-0.559	Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	I
G/L	0.9488	likely_pathogenic	0.9419	pathogenic	-0.538	Destabilizing	1.0	D	0.826	deleterious	None	None	None	None	I
G/M	0.9604	likely_pathogenic	0.958	pathogenic	-0.648	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	I
G/N	0.8748	likely_pathogenic	0.8651	pathogenic	-0.317	Destabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	I
G/P	0.9924	likely_pathogenic	0.9892	pathogenic	-0.43	Destabilizing	1.0	D	0.822	deleterious	None	None	None	None	I
G/Q	0.9194	likely_pathogenic	0.9226	pathogenic	-0.55	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	I
G/R	0.8914	likely_pathogenic	0.9053	pathogenic	-0.202	Destabilizing	1.0	D	0.823	deleterious	N	0.503723543	None	None	I
G/S	0.5464	ambiguous	0.5138	ambiguous	-0.482	Destabilizing	1.0	D	0.731	prob.delet.	N	0.494351793	None	None	I
G/T	0.8667	likely_pathogenic	0.8545	pathogenic	-0.562	Destabilizing	1.0	D	0.818	deleterious	None	None	None	None	I
G/V	0.9178	likely_pathogenic	0.9132	pathogenic	-0.43	Destabilizing	1.0	D	0.815	deleterious	D	0.526347248	None	None	I
G/W	0.943	likely_pathogenic	0.9513	pathogenic	-1.092	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	I
G/Y	0.9453	likely_pathogenic	0.9441	pathogenic	-0.8	Destabilizing	1.0	D	0.8	deleterious	None	None	None	None	I

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.