TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8448	25567;25568;25569	chr2:178717532;178717531;178717530	chr2:179582259;179582258;179582257
N2AB	8131	24616;24617;24618	chr2:178717532;178717531;178717530	chr2:179582259;179582258;179582257
N2A	7204	21835;21836;21837	chr2:178717532;178717531;178717530	chr2:179582259;179582258;179582257
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: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Ig-69
• Domain position: 89
• Structural Position: 175
• Q(SASA): 0.3644
• 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
I/T	rs2077674998	None	None	N	0.109	0.069	0.224531998449	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
I/T	rs2077674998	None	None	N	0.109	0.069	0.224531998449	gnomAD-4.0.0	6.57108E-06	None	None	None	None	N	None	2.41185E-05	0	None	0	0	None	0	0	0	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
I/A	0.3144	likely_benign	0.284	benign	-1.816	Destabilizing	0.004	N	0.234	neutral	None	None	None	None	N
I/C	0.6652	likely_pathogenic	0.6283	pathogenic	-0.965	Destabilizing	0.245	N	0.411	neutral	None	None	None	None	N
I/D	0.5673	likely_pathogenic	0.5254	ambiguous	-1.336	Destabilizing	0.009	N	0.407	neutral	None	None	None	None	N
I/E	0.4509	ambiguous	0.405	ambiguous	-1.296	Destabilizing	None	N	0.224	neutral	None	None	None	None	N
I/F	0.1077	likely_benign	0.1035	benign	-1.182	Destabilizing	0.017	N	0.313	neutral	N	0.438698771	None	None	N
I/G	0.5899	likely_pathogenic	0.5472	ambiguous	-2.183	Highly Destabilizing	0.018	N	0.412	neutral	None	None	None	None	N
I/H	0.2718	likely_benign	0.2569	benign	-1.368	Destabilizing	0.245	N	0.467	neutral	None	None	None	None	N
I/K	0.2764	likely_benign	0.2453	benign	-1.295	Destabilizing	0.009	N	0.431	neutral	None	None	None	None	N
I/L	0.0834	likely_benign	0.0795	benign	-0.859	Destabilizing	None	N	0.051	neutral	N	0.458101481	None	None	N
I/M	0.0963	likely_benign	0.0965	benign	-0.61	Destabilizing	0.108	N	0.321	neutral	N	0.489117821	None	None	N
I/N	0.18	likely_benign	0.1701	benign	-1.139	Destabilizing	0.033	N	0.471	neutral	N	0.475764522	None	None	N
I/P	0.8787	likely_pathogenic	0.8245	pathogenic	-1.148	Destabilizing	0.085	N	0.516	neutral	None	None	None	None	N
I/Q	0.2674	likely_benign	0.2446	benign	-1.273	Destabilizing	0.001	N	0.273	neutral	None	None	None	None	N
I/R	0.197	likely_benign	0.1753	benign	-0.701	Destabilizing	0.022	N	0.523	neutral	None	None	None	None	N
I/S	0.2025	likely_benign	0.1892	benign	-1.765	Destabilizing	0.001	N	0.166	neutral	N	0.46949191	None	None	N
I/T	0.1639	likely_benign	0.1501	benign	-1.607	Destabilizing	None	N	0.109	neutral	N	0.396300874	None	None	N
I/V	0.0913	likely_benign	0.0885	benign	-1.148	Destabilizing	None	N	0.054	neutral	N	0.42298883	None	None	N
I/W	0.623	likely_pathogenic	0.5869	pathogenic	-1.313	Destabilizing	0.788	D	0.46	neutral	None	None	None	None	N
I/Y	0.3297	likely_benign	0.3178	benign	-1.09	Destabilizing	0.085	N	0.479	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.