TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28810	86653;86654;86655	chr2:178559704;178559703;178559702	chr2:179424431;179424430;179424429
N2AB	27169	81730;81731;81732	chr2:178559704;178559703;178559702	chr2:179424431;179424430;179424429
N2A	26242	78949;78950;78951	chr2:178559704;178559703;178559702	chr2:179424431;179424430;179424429
N2B	19745	59458;59459;59460	chr2:178559704;178559703;178559702	chr2:179424431;179424430;179424429
Novex-1	19870	59833;59834;59835	chr2:178559704;178559703;178559702	chr2:179424431;179424430;179424429
Novex-2	19937	60034;60035;60036	chr2:178559704;178559703;178559702	chr2:179424431;179424430;179424429
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTG
• RefSeq wild type template codon: GAC
• Domain: Ig-144
• Domain position: 56
• Structural Position: 138
• Q(SASA): 0.1264
• 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
L/V	None	None	0.248	N	0.39	0.333	0.56731557318	gnomAD-4.0.0	2.06226E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.70698E-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
L/A	0.9274	likely_pathogenic	0.9178	pathogenic	-2.148	Highly Destabilizing	0.97	D	0.701	prob.neutral	None	None	None	None	N
L/C	0.8336	likely_pathogenic	0.8289	pathogenic	-1.615	Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	N
L/D	0.9996	likely_pathogenic	0.9996	pathogenic	-2.861	Highly Destabilizing	0.999	D	0.834	deleterious	None	None	None	None	N
L/E	0.9967	likely_pathogenic	0.997	pathogenic	-2.532	Highly Destabilizing	0.999	D	0.843	deleterious	None	None	None	None	N
L/F	0.3708	ambiguous	0.3384	benign	-1.316	Destabilizing	0.996	D	0.686	prob.neutral	None	None	None	None	N
L/G	0.9925	likely_pathogenic	0.9915	pathogenic	-2.77	Highly Destabilizing	0.999	D	0.841	deleterious	None	None	None	None	N
L/H	0.9858	likely_pathogenic	0.9858	pathogenic	-2.752	Highly Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
L/I	0.1208	likely_benign	0.117	benign	-0.285	Destabilizing	0.155	N	0.329	neutral	None	None	None	None	N
L/K	0.9936	likely_pathogenic	0.9941	pathogenic	-1.503	Destabilizing	0.999	D	0.813	deleterious	None	None	None	None	N
L/M	0.2126	likely_benign	0.1876	benign	-0.604	Destabilizing	0.994	D	0.678	prob.neutral	N	0.514305467	None	None	N
L/N	0.9967	likely_pathogenic	0.9966	pathogenic	-2.222	Highly Destabilizing	0.999	D	0.825	deleterious	None	None	None	None	N
L/P	0.9982	likely_pathogenic	0.9981	pathogenic	-0.895	Destabilizing	0.998	D	0.827	deleterious	D	0.553680756	None	None	N
L/Q	0.9827	likely_pathogenic	0.983	pathogenic	-1.812	Destabilizing	0.998	D	0.813	deleterious	D	0.553680756	None	None	N
L/R	0.9861	likely_pathogenic	0.9874	pathogenic	-1.81	Destabilizing	0.998	D	0.798	deleterious	D	0.54232445	None	None	N
L/S	0.9916	likely_pathogenic	0.9903	pathogenic	-2.785	Highly Destabilizing	0.996	D	0.795	deleterious	None	None	None	None	N
L/T	0.9681	likely_pathogenic	0.9656	pathogenic	-2.273	Highly Destabilizing	0.97	D	0.735	prob.delet.	None	None	None	None	N
L/V	0.1406	likely_benign	0.1422	benign	-0.895	Destabilizing	0.248	N	0.39	neutral	N	0.499568574	None	None	N
L/W	0.9351	likely_pathogenic	0.9312	pathogenic	-1.744	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
L/Y	0.9358	likely_pathogenic	0.9285	pathogenic	-1.445	Destabilizing	0.999	D	0.723	prob.delet.	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.