TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15086	45481;45482;45483	chr2:178621568;178621567;178621566	chr2:179486295;179486294;179486293
N2AB	13445	40558;40559;40560	chr2:178621568;178621567;178621566	chr2:179486295;179486294;179486293
N2A	12518	37777;37778;37779	chr2:178621568;178621567;178621566	chr2:179486295;179486294;179486293
N2B	6021	18286;18287;18288	chr2:178621568;178621567;178621566	chr2:179486295;179486294;179486293
Novex-1	6146	18661;18662;18663	chr2:178621568;178621567;178621566	chr2:179486295;179486294;179486293
Novex-2	6213	18862;18863;18864	chr2:178621568;178621567;178621566	chr2:179486295;179486294;179486293
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-102
• Domain position: 56
• Structural Position: 137
• Q(SASA): 0.1018
• 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
I/V	None	None	0.141	N	0.444	0.116	0.542630587416	gnomAD-4.0.0	1.59385E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86292E-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	0.5657	likely_pathogenic	0.574	pathogenic	-2.814	Highly Destabilizing	0.547	D	0.599	neutral	None	None	None	None	N
I/C	0.7654	likely_pathogenic	0.7943	pathogenic	-1.846	Destabilizing	0.985	D	0.709	prob.delet.	None	None	None	None	N
I/D	0.8824	likely_pathogenic	0.8598	pathogenic	-3.483	Highly Destabilizing	0.894	D	0.776	deleterious	None	None	None	None	N
I/E	0.6959	likely_pathogenic	0.6914	pathogenic	-3.219	Highly Destabilizing	0.894	D	0.773	deleterious	None	None	None	None	N
I/F	0.1994	likely_benign	0.2139	benign	-1.719	Destabilizing	0.928	D	0.641	neutral	N	0.509188538	None	None	N
I/G	0.8171	likely_pathogenic	0.8154	pathogenic	-3.357	Highly Destabilizing	0.894	D	0.747	deleterious	None	None	None	None	N
I/H	0.5574	ambiguous	0.5841	pathogenic	-2.9	Highly Destabilizing	0.995	D	0.785	deleterious	None	None	None	None	N
I/K	0.5734	likely_pathogenic	0.5646	pathogenic	-2.317	Highly Destabilizing	0.894	D	0.777	deleterious	None	None	None	None	N
I/L	0.178	likely_benign	0.1791	benign	-1.201	Destabilizing	0.273	N	0.446	neutral	N	0.501023868	None	None	N
I/M	0.1345	likely_benign	0.1375	benign	-1.084	Destabilizing	0.928	D	0.65	neutral	N	0.504190425	None	None	N
I/N	0.3979	ambiguous	0.3618	ambiguous	-2.814	Highly Destabilizing	0.864	D	0.781	deleterious	N	0.501023868	None	None	N
I/P	0.9885	likely_pathogenic	0.9838	pathogenic	-1.727	Destabilizing	0.945	D	0.801	deleterious	None	None	None	None	N
I/Q	0.5533	ambiguous	0.5706	pathogenic	-2.61	Highly Destabilizing	0.945	D	0.809	deleterious	None	None	None	None	N
I/R	0.4645	ambiguous	0.4664	ambiguous	-2.044	Highly Destabilizing	0.894	D	0.801	deleterious	None	None	None	None	N
I/S	0.3994	ambiguous	0.3945	ambiguous	-3.391	Highly Destabilizing	0.477	N	0.693	prob.neutral	N	0.473603554	None	None	N
I/T	0.362	ambiguous	0.3496	ambiguous	-2.995	Highly Destabilizing	0.006	N	0.449	neutral	N	0.467293968	None	None	N
I/V	0.1176	likely_benign	0.1052	benign	-1.727	Destabilizing	0.141	N	0.444	neutral	N	0.506989142	None	None	N
I/W	0.7918	likely_pathogenic	0.81	pathogenic	-2.21	Highly Destabilizing	0.995	D	0.753	deleterious	None	None	None	None	N
I/Y	0.4513	ambiguous	0.4892	ambiguous	-1.942	Destabilizing	0.945	D	0.741	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.