TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16839	50740;50741;50742	chr2:178611794;178611793;178611792	chr2:179476521;179476520;179476519
N2AB	15198	45817;45818;45819	chr2:178611794;178611793;178611792	chr2:179476521;179476520;179476519
N2A	14271	43036;43037;43038	chr2:178611794;178611793;178611792	chr2:179476521;179476520;179476519
N2B	7774	23545;23546;23547	chr2:178611794;178611793;178611792	chr2:179476521;179476520;179476519
Novex-1	7899	23920;23921;23922	chr2:178611794;178611793;178611792	chr2:179476521;179476520;179476519
Novex-2	7966	24121;24122;24123	chr2:178611794;178611793;178611792	chr2:179476521;179476520;179476519
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: Fn3-10
• Domain position: 89
• Structural Position: 122
• Q(SASA): 0.4779
• 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/V	None	None	0.857	N	0.694	0.239	0.427713192076	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.66327E-05

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	0.474	ambiguous	0.3807	ambiguous	-0.111	Destabilizing	0.297	N	0.647	neutral	N	0.474768852	None	None	N
E/C	0.9768	likely_pathogenic	0.9674	pathogenic	-0.148	Destabilizing	0.989	D	0.763	deleterious	None	None	None	None	N
E/D	0.2639	likely_benign	0.2656	benign	-0.283	Destabilizing	0.457	N	0.655	prob.neutral	N	0.476249102	None	None	N
E/F	0.9552	likely_pathogenic	0.9334	pathogenic	-0.073	Destabilizing	0.989	D	0.723	deleterious	None	None	None	None	N
E/G	0.551	ambiguous	0.4762	ambiguous	-0.25	Destabilizing	0.003	N	0.532	neutral	N	0.494269422	None	None	N
E/H	0.9018	likely_pathogenic	0.847	pathogenic	0.462	Stabilizing	0.989	D	0.627	neutral	None	None	None	None	N
E/I	0.7558	likely_pathogenic	0.6642	pathogenic	0.203	Stabilizing	0.888	D	0.732	deleterious	None	None	None	None	N
E/K	0.5678	likely_pathogenic	0.4102	ambiguous	0.435	Stabilizing	0.457	N	0.622	neutral	N	0.473914987	None	None	N
E/L	0.7759	likely_pathogenic	0.6882	pathogenic	0.203	Stabilizing	0.888	D	0.703	prob.delet.	None	None	None	None	N
E/M	0.8256	likely_pathogenic	0.737	pathogenic	0.048	Stabilizing	0.989	D	0.757	deleterious	None	None	None	None	N
E/N	0.6872	likely_pathogenic	0.623	pathogenic	0.129	Stabilizing	0.797	D	0.618	neutral	None	None	None	None	N
E/P	0.767	likely_pathogenic	0.6909	pathogenic	0.117	Stabilizing	0.888	D	0.627	neutral	None	None	None	None	N
E/Q	0.4566	ambiguous	0.3428	ambiguous	0.151	Stabilizing	0.857	D	0.629	neutral	N	0.493302473	None	None	N
E/R	0.7578	likely_pathogenic	0.6321	pathogenic	0.675	Stabilizing	0.888	D	0.605	neutral	None	None	None	None	N
E/S	0.5617	ambiguous	0.4938	ambiguous	-0.007	Destabilizing	0.359	N	0.622	neutral	None	None	None	None	N
E/T	0.6383	likely_pathogenic	0.5602	ambiguous	0.115	Stabilizing	0.797	D	0.592	neutral	None	None	None	None	N
E/V	0.5919	likely_pathogenic	0.472	ambiguous	0.117	Stabilizing	0.857	D	0.694	prob.delet.	N	0.468758841	None	None	N
E/W	0.9915	likely_pathogenic	0.9874	pathogenic	0.014	Stabilizing	0.989	D	0.761	deleterious	None	None	None	None	N
E/Y	0.9268	likely_pathogenic	0.8982	pathogenic	0.161	Stabilizing	0.96	D	0.731	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.