TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7935	24028;24029;24030	chr2:178719689;178719688;178719687	chr2:179584416;179584415;179584414
N2AB	7618	23077;23078;23079	chr2:178719689;178719688;178719687	chr2:179584416;179584415;179584414
N2A	6691	20296;20297;20298	chr2:178719689;178719688;178719687	chr2:179584416;179584415;179584414
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: H
• RefSeq wild type transcript codon: CAT
• RefSeq wild type template codon: GTA
• Domain: Ig-64
• Domain position: 47
• Structural Position: 121
• Q(SASA): 0.1759
• 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
H/Y	None	None	0.002	N	0.178	0.186	0.233150807113	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
H/A	0.5022	ambiguous	0.5878	pathogenic	-1.525	Destabilizing	0.495	N	0.563	neutral	None	None	None	None	N
H/C	0.1891	likely_benign	0.2162	benign	-0.753	Destabilizing	0.007	N	0.597	neutral	None	None	None	None	N
H/D	0.5303	ambiguous	0.593	pathogenic	-1.42	Destabilizing	0.642	D	0.655	neutral	D	0.530653957	None	None	N
H/E	0.5295	ambiguous	0.6175	pathogenic	-1.251	Destabilizing	0.329	N	0.457	neutral	None	None	None	None	N
H/F	0.2813	likely_benign	0.3006	benign	0.212	Stabilizing	0.543	D	0.655	neutral	None	None	None	None	N
H/G	0.4811	ambiguous	0.5421	ambiguous	-1.954	Destabilizing	0.828	D	0.627	neutral	None	None	None	None	N
H/I	0.3728	ambiguous	0.4383	ambiguous	-0.276	Destabilizing	0.704	D	0.675	prob.neutral	None	None	None	None	N
H/K	0.3637	ambiguous	0.4721	ambiguous	-1.12	Destabilizing	0.543	D	0.627	neutral	None	None	None	None	N
H/L	0.1614	likely_benign	0.1921	benign	-0.276	Destabilizing	0.27	N	0.595	neutral	N	0.51468164	None	None	N
H/M	0.5607	ambiguous	0.6107	pathogenic	-0.459	Destabilizing	0.981	D	0.644	neutral	None	None	None	None	N
H/N	0.1618	likely_benign	0.1761	benign	-1.541	Destabilizing	0.784	D	0.549	neutral	N	0.484491469	None	None	N
H/P	0.5266	ambiguous	0.6106	pathogenic	-0.679	Destabilizing	0.975	D	0.684	prob.neutral	N	0.484744958	None	None	N
H/Q	0.2451	likely_benign	0.2937	benign	-1.137	Destabilizing	0.065	N	0.321	neutral	N	0.489264409	None	None	N
H/R	0.1346	likely_benign	0.165	benign	-1.581	Destabilizing	0.642	D	0.578	neutral	N	0.521957116	None	None	N
H/S	0.3696	ambiguous	0.4279	ambiguous	-1.616	Destabilizing	0.704	D	0.617	neutral	None	None	None	None	N
H/T	0.3782	ambiguous	0.4504	ambiguous	-1.329	Destabilizing	0.828	D	0.639	neutral	None	None	None	None	N
H/V	0.3278	likely_benign	0.3917	ambiguous	-0.679	Destabilizing	0.704	D	0.639	neutral	None	None	None	None	N
H/W	0.3534	ambiguous	0.3694	ambiguous	0.634	Stabilizing	0.985	D	0.637	neutral	None	None	None	None	N
H/Y	0.0648	likely_benign	0.0634	benign	0.534	Stabilizing	0.002	N	0.178	neutral	N	0.394296876	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.