TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15034	45325;45326;45327	chr2:178621724;178621723;178621722	chr2:179486451;179486450;179486449
N2AB	13393	40402;40403;40404	chr2:178621724;178621723;178621722	chr2:179486451;179486450;179486449
N2A	12466	37621;37622;37623	chr2:178621724;178621723;178621722	chr2:179486451;179486450;179486449
N2B	5969	18130;18131;18132	chr2:178621724;178621723;178621722	chr2:179486451;179486450;179486449
Novex-1	6094	18505;18506;18507	chr2:178621724;178621723;178621722	chr2:179486451;179486450;179486449
Novex-2	6161	18706;18707;18708	chr2:178621724;178621723;178621722	chr2:179486451;179486450;179486449
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Ig-102
• Domain position: 4
• Structural Position: 4
• Q(SASA): 0.448
• 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
T/A	None	None	0.981	D	0.464	0.579	0.635921679534	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	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
T/A	0.1314	likely_benign	0.1444	benign	-0.666	Destabilizing	0.981	D	0.464	neutral	D	0.650316825	None	None	N
T/C	0.6097	likely_pathogenic	0.6555	pathogenic	-0.399	Destabilizing	1.0	D	0.697	prob.neutral	None	None	None	None	N
T/D	0.6314	likely_pathogenic	0.7099	pathogenic	0.159	Stabilizing	0.999	D	0.703	prob.neutral	None	None	None	None	N
T/E	0.4488	ambiguous	0.5253	ambiguous	0.145	Stabilizing	0.999	D	0.701	prob.neutral	None	None	None	None	N
T/F	0.4083	ambiguous	0.4561	ambiguous	-0.777	Destabilizing	1.0	D	0.749	deleterious	None	None	None	None	N
T/G	0.3559	ambiguous	0.4195	ambiguous	-0.905	Destabilizing	0.997	D	0.613	neutral	None	None	None	None	N
T/H	0.4065	ambiguous	0.4593	ambiguous	-1.13	Destabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	N
T/I	0.194	likely_benign	0.2334	benign	-0.131	Destabilizing	0.999	D	0.74	deleterious	D	0.540305241	None	None	N
T/K	0.2784	likely_benign	0.3474	ambiguous	-0.568	Destabilizing	0.999	D	0.708	prob.delet.	None	None	None	None	N
T/L	0.107	likely_benign	0.1354	benign	-0.131	Destabilizing	0.998	D	0.639	neutral	None	None	None	None	N
T/M	0.132	likely_benign	0.1393	benign	0.052	Stabilizing	1.0	D	0.713	prob.delet.	None	None	None	None	N
T/N	0.2024	likely_benign	0.2444	benign	-0.451	Destabilizing	0.999	D	0.675	prob.neutral	D	0.687038432	None	None	N
T/P	0.3271	likely_benign	0.3426	ambiguous	-0.277	Destabilizing	0.999	D	0.736	prob.delet.	D	0.762396423	None	None	N
T/Q	0.297	likely_benign	0.3368	benign	-0.606	Destabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	N
T/R	0.2345	likely_benign	0.2663	benign	-0.338	Destabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	N
T/S	0.1511	likely_benign	0.1694	benign	-0.762	Destabilizing	0.905	D	0.275	neutral	D	0.644070135	None	None	N
T/V	0.1635	likely_benign	0.1936	benign	-0.277	Destabilizing	0.998	D	0.569	neutral	None	None	None	None	N
T/W	0.7587	likely_pathogenic	0.7971	pathogenic	-0.715	Destabilizing	1.0	D	0.745	deleterious	None	None	None	None	N
T/Y	0.4986	ambiguous	0.549	ambiguous	-0.479	Destabilizing	1.0	D	0.743	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.