TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28932	87019;87020;87021	chr2:178559338;178559337;178559336	chr2:179424065;179424064;179424063
N2AB	27291	82096;82097;82098	chr2:178559338;178559337;178559336	chr2:179424065;179424064;179424063
N2A	26364	79315;79316;79317	chr2:178559338;178559337;178559336	chr2:179424065;179424064;179424063
N2B	19867	59824;59825;59826	chr2:178559338;178559337;178559336	chr2:179424065;179424064;179424063
Novex-1	19992	60199;60200;60201	chr2:178559338;178559337;178559336	chr2:179424065;179424064;179424063
Novex-2	20059	60400;60401;60402	chr2:178559338;178559337;178559336	chr2:179424065;179424064;179424063
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-98
• Domain position: 88
• Structural Position: 122
• Q(SASA): 0.4626
• 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
E/A	rs1702752207	None	0.613	N	0.761	0.277	0.387042434762	gnomAD-4.0.0	1.20035E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.31253E-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
E/A	0.3298	likely_benign	0.3122	benign	-0.699	Destabilizing	0.613	D	0.761	deleterious	N	0.475137312	None	None	N
E/C	0.9271	likely_pathogenic	0.9189	pathogenic	-0.398	Destabilizing	0.994	D	0.813	deleterious	None	None	None	None	N
E/D	0.2362	likely_benign	0.2504	benign	-0.984	Destabilizing	0.001	N	0.321	neutral	N	0.463869912	None	None	N
E/F	0.8827	likely_pathogenic	0.8574	pathogenic	0.224	Stabilizing	0.997	D	0.849	deleterious	None	None	None	None	N
E/G	0.4649	ambiguous	0.4655	ambiguous	-1.106	Destabilizing	0.949	D	0.787	deleterious	N	0.488775023	None	None	N
E/H	0.779	likely_pathogenic	0.7529	pathogenic	0.066	Stabilizing	0.996	D	0.781	deleterious	None	None	None	None	N
E/I	0.5091	ambiguous	0.4884	ambiguous	0.427	Stabilizing	0.928	D	0.82	deleterious	None	None	None	None	N
E/K	0.4421	ambiguous	0.4286	ambiguous	-0.434	Destabilizing	0.746	D	0.745	deleterious	N	0.475581839	None	None	N
E/L	0.6188	likely_pathogenic	0.6033	pathogenic	0.427	Stabilizing	0.928	D	0.758	deleterious	None	None	None	None	N
E/M	0.6323	likely_pathogenic	0.5936	pathogenic	0.778	Stabilizing	0.964	D	0.847	deleterious	None	None	None	None	N
E/N	0.5295	ambiguous	0.5251	ambiguous	-1.076	Destabilizing	0.598	D	0.803	deleterious	None	None	None	None	N
E/P	0.8614	likely_pathogenic	0.8796	pathogenic	0.073	Stabilizing	0.658	D	0.779	deleterious	None	None	None	None	N
E/Q	0.2928	likely_benign	0.2861	benign	-0.897	Destabilizing	0.88	D	0.787	deleterious	N	0.470163789	None	None	N
E/R	0.6438	likely_pathogenic	0.6365	pathogenic	-0.053	Destabilizing	0.965	D	0.787	deleterious	None	None	None	None	N
E/S	0.4143	ambiguous	0.4073	ambiguous	-1.419	Destabilizing	0.512	D	0.751	deleterious	None	None	None	None	N
E/T	0.4165	ambiguous	0.3888	ambiguous	-1.067	Destabilizing	0.911	D	0.751	deleterious	None	None	None	None	N
E/V	0.3187	likely_benign	0.2916	benign	0.073	Stabilizing	0.874	D	0.773	deleterious	N	0.465555433	None	None	N
E/W	0.9721	likely_pathogenic	0.9684	pathogenic	0.566	Stabilizing	0.999	D	0.829	deleterious	None	None	None	None	N
E/Y	0.8384	likely_pathogenic	0.8244	pathogenic	0.52	Stabilizing	0.999	D	0.845	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.