TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16904	50935;50936;50937	chr2:178611519;178611518;178611517	chr2:179476246;179476245;179476244
N2AB	15263	46012;46013;46014	chr2:178611519;178611518;178611517	chr2:179476246;179476245;179476244
N2A	14336	43231;43232;43233	chr2:178611519;178611518;178611517	chr2:179476246;179476245;179476244
N2B	7839	23740;23741;23742	chr2:178611519;178611518;178611517	chr2:179476246;179476245;179476244
Novex-1	7964	24115;24116;24117	chr2:178611519;178611518;178611517	chr2:179476246;179476245;179476244
Novex-2	8031	24316;24317;24318	chr2:178611519;178611518;178611517	chr2:179476246;179476245;179476244
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCT
• RefSeq wild type template codon: AGA
• Domain: Fn3-11
• Domain position: 53
• Structural Position: 70
• Q(SASA): 0.6002
• 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
S/P	None	None	1.0	N	0.727	0.435	0.392395365052	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
S/A	0.0977	likely_benign	0.0929	benign	-0.173	Destabilizing	0.997	D	0.44	neutral	N	0.466367	None	None	I
S/C	0.2124	likely_benign	0.2017	benign	-0.362	Destabilizing	1.0	D	0.705	prob.neutral	D	0.5417299	None	None	I
S/D	0.6622	likely_pathogenic	0.612	pathogenic	0.003	Stabilizing	0.999	D	0.592	neutral	None	None	None	None	I
S/E	0.7164	likely_pathogenic	0.6956	pathogenic	-0.108	Destabilizing	0.999	D	0.575	neutral	None	None	None	None	I
S/F	0.4789	ambiguous	0.4508	ambiguous	-0.884	Destabilizing	1.0	D	0.745	deleterious	N	0.482538257	None	None	I
S/G	0.1257	likely_benign	0.138	benign	-0.227	Destabilizing	0.999	D	0.474	neutral	None	None	None	None	I
S/H	0.5448	ambiguous	0.5561	ambiguous	-0.592	Destabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	I
S/I	0.344	ambiguous	0.3472	ambiguous	-0.164	Destabilizing	1.0	D	0.724	prob.delet.	None	None	None	None	I
S/K	0.8554	likely_pathogenic	0.8396	pathogenic	-0.437	Destabilizing	0.999	D	0.578	neutral	None	None	None	None	I
S/L	0.1895	likely_benign	0.1718	benign	-0.164	Destabilizing	1.0	D	0.684	prob.neutral	None	None	None	None	I
S/M	0.3316	likely_benign	0.3433	ambiguous	-0.106	Destabilizing	1.0	D	0.726	prob.delet.	None	None	None	None	I
S/N	0.2151	likely_benign	0.2124	benign	-0.187	Destabilizing	0.999	D	0.563	neutral	None	None	None	None	I
S/P	0.1901	likely_benign	0.1819	benign	-0.141	Destabilizing	1.0	D	0.727	prob.delet.	N	0.468687668	None	None	I
S/Q	0.6127	likely_pathogenic	0.6418	pathogenic	-0.427	Destabilizing	1.0	D	0.697	prob.neutral	None	None	None	None	I
S/R	0.8232	likely_pathogenic	0.8061	pathogenic	-0.176	Destabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	I
S/T	0.1266	likely_benign	0.116	benign	-0.292	Destabilizing	0.999	D	0.458	neutral	N	0.459723663	None	None	I
S/V	0.3127	likely_benign	0.314	benign	-0.141	Destabilizing	1.0	D	0.744	deleterious	None	None	None	None	I
S/W	0.601	likely_pathogenic	0.6201	pathogenic	-0.96	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	I
S/Y	0.4052	ambiguous	0.3985	ambiguous	-0.651	Destabilizing	1.0	D	0.736	prob.delet.	N	0.476369479	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.