TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21549	64870;64871;64872	chr2:178585099;178585098;178585097	chr2:179449826;179449825;179449824
N2AB	19908	59947;59948;59949	chr2:178585099;178585098;178585097	chr2:179449826;179449825;179449824
N2A	18981	57166;57167;57168	chr2:178585099;178585098;178585097	chr2:179449826;179449825;179449824
N2B	12484	37675;37676;37677	chr2:178585099;178585098;178585097	chr2:179449826;179449825;179449824
Novex-1	12609	38050;38051;38052	chr2:178585099;178585098;178585097	chr2:179449826;179449825;179449824
Novex-2	12676	38251;38252;38253	chr2:178585099;178585098;178585097	chr2:179449826;179449825;179449824
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Ig-124
• Domain position: 81
• Structural Position: 168
• Q(SASA): 0.2804
• 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/P	None	None	0.966	D	0.538	0.411	0.443797312901	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	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
T/A	0.0996	likely_benign	0.0916	benign	-0.778	Destabilizing	0.454	N	0.467	neutral	N	0.506702449	None	None	N
T/C	0.2675	likely_benign	0.2383	benign	-0.448	Destabilizing	0.998	D	0.517	neutral	None	None	None	None	N
T/D	0.3969	ambiguous	0.3774	ambiguous	-0.376	Destabilizing	0.728	D	0.523	neutral	None	None	None	None	N
T/E	0.2803	likely_benign	0.2752	benign	-0.414	Destabilizing	0.842	D	0.511	neutral	None	None	None	None	N
T/F	0.2025	likely_benign	0.1754	benign	-1.013	Destabilizing	0.991	D	0.603	neutral	None	None	None	None	N
T/G	0.2698	likely_benign	0.2485	benign	-0.99	Destabilizing	0.525	D	0.547	neutral	None	None	None	None	N
T/H	0.196	likely_benign	0.1874	benign	-1.321	Destabilizing	0.974	D	0.59	neutral	None	None	None	None	N
T/I	0.1151	likely_benign	0.104	benign	-0.314	Destabilizing	0.966	D	0.539	neutral	D	0.522826695	None	None	N
T/K	0.2124	likely_benign	0.2016	benign	-0.768	Destabilizing	0.842	D	0.508	neutral	None	None	None	None	N
T/L	0.1134	likely_benign	0.1011	benign	-0.314	Destabilizing	0.842	D	0.507	neutral	None	None	None	None	N
T/M	0.0926	likely_benign	0.0885	benign	0.094	Stabilizing	0.998	D	0.519	neutral	None	None	None	None	N
T/N	0.1346	likely_benign	0.1207	benign	-0.623	Destabilizing	0.022	N	0.154	neutral	N	0.469338926	None	None	N
T/P	0.5448	ambiguous	0.6272	pathogenic	-0.438	Destabilizing	0.966	D	0.538	neutral	D	0.535486561	None	None	N
T/Q	0.1885	likely_benign	0.1867	benign	-0.885	Destabilizing	0.974	D	0.543	neutral	None	None	None	None	N
T/R	0.1811	likely_benign	0.1706	benign	-0.439	Destabilizing	0.949	D	0.528	neutral	None	None	None	None	N
T/S	0.0986	likely_benign	0.0942	benign	-0.86	Destabilizing	0.022	N	0.154	neutral	N	0.455214836	None	None	N
T/V	0.0991	likely_benign	0.0925	benign	-0.438	Destabilizing	0.842	D	0.471	neutral	None	None	None	None	N
T/W	0.5744	likely_pathogenic	0.575	pathogenic	-0.934	Destabilizing	0.998	D	0.655	neutral	None	None	None	None	N
T/Y	0.2443	likely_benign	0.2091	benign	-0.709	Destabilizing	0.991	D	0.6	neutral	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.