TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5668	17227;17228;17229	chr2:178731873;178731872;178731871	chr2:179596600;179596599;179596598
N2AB	5351	16276;16277;16278	chr2:178731873;178731872;178731871	chr2:179596600;179596599;179596598
N2A	4424	13495;13496;13497	chr2:178731873;178731872;178731871	chr2:179596600;179596599;179596598
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Ig-40
• Domain position: 32
• Structural Position: 46
• Q(SASA): 0.221
• 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
I/N	None	None	0.989	D	0.84	0.702	0.909692242837	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-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
I/A	0.5234	ambiguous	0.5433	ambiguous	-1.953	Destabilizing	0.525	D	0.651	neutral	None	None	None	None	I
I/C	0.7378	likely_pathogenic	0.7413	pathogenic	-1.093	Destabilizing	0.998	D	0.717	prob.delet.	None	None	None	None	I
I/D	0.8897	likely_pathogenic	0.9201	pathogenic	-1.515	Destabilizing	0.991	D	0.846	deleterious	None	None	None	None	I
I/E	0.8102	likely_pathogenic	0.8504	pathogenic	-1.444	Destabilizing	0.974	D	0.825	deleterious	None	None	None	None	I
I/F	0.2131	likely_benign	0.2501	benign	-1.267	Destabilizing	0.934	D	0.684	prob.neutral	D	0.539799089	None	None	I
I/G	0.8155	likely_pathogenic	0.8343	pathogenic	-2.354	Highly Destabilizing	0.974	D	0.823	deleterious	None	None	None	None	I
I/H	0.7794	likely_pathogenic	0.8205	pathogenic	-1.595	Destabilizing	0.998	D	0.83	deleterious	None	None	None	None	I
I/K	0.6513	likely_pathogenic	0.7104	pathogenic	-1.377	Destabilizing	0.974	D	0.827	deleterious	None	None	None	None	I
I/L	0.1709	likely_benign	0.179	benign	-0.881	Destabilizing	0.005	N	0.29	neutral	D	0.538758939	None	None	I
I/M	0.106	likely_benign	0.1146	benign	-0.654	Destabilizing	0.934	D	0.637	neutral	D	0.526204751	None	None	I
I/N	0.4966	ambiguous	0.5568	ambiguous	-1.257	Destabilizing	0.989	D	0.84	deleterious	D	0.5446514	None	None	I
I/P	0.8475	likely_pathogenic	0.8461	pathogenic	-1.21	Destabilizing	0.991	D	0.845	deleterious	None	None	None	None	I
I/Q	0.7266	likely_pathogenic	0.7772	pathogenic	-1.346	Destabilizing	0.991	D	0.841	deleterious	None	None	None	None	I
I/R	0.6193	likely_pathogenic	0.6931	pathogenic	-0.856	Destabilizing	0.974	D	0.84	deleterious	None	None	None	None	I
I/S	0.5527	ambiguous	0.5976	pathogenic	-1.906	Destabilizing	0.966	D	0.81	deleterious	N	0.510164411	None	None	I
I/T	0.4087	ambiguous	0.4623	ambiguous	-1.706	Destabilizing	0.801	D	0.713	prob.delet.	N	0.514683861	None	None	I
I/V	0.0759	likely_benign	0.0787	benign	-1.21	Destabilizing	0.002	N	0.229	neutral	N	0.43963959	None	None	I
I/W	0.8578	likely_pathogenic	0.8838	pathogenic	-1.424	Destabilizing	0.998	D	0.844	deleterious	None	None	None	None	I
I/Y	0.5967	likely_pathogenic	0.6331	pathogenic	-1.191	Destabilizing	0.974	D	0.747	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.