TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26951	81076;81077;81078	chr2:178565281;178565280;178565279	chr2:179430008;179430007;179430006
N2AB	25310	76153;76154;76155	chr2:178565281;178565280;178565279	chr2:179430008;179430007;179430006
N2A	24383	73372;73373;73374	chr2:178565281;178565280;178565279	chr2:179430008;179430007;179430006
N2B	17886	53881;53882;53883	chr2:178565281;178565280;178565279	chr2:179430008;179430007;179430006
Novex-1	18011	54256;54257;54258	chr2:178565281;178565280;178565279	chr2:179430008;179430007;179430006
Novex-2	18078	54457;54458;54459	chr2:178565281;178565280;178565279	chr2:179430008;179430007;179430006
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-139
• Domain position: 72
• Structural Position: 155
• Q(SASA): 0.1659
• 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/I	None	None	0.055	N	0.601	0.07	0.198526703765	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	6.33473E-05	0	None	0	0	None	0	0	0	0	0
T/N	None	None	0.029	N	0.464	0.147	0.209622950755	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	0.0737	likely_benign	0.0721	benign	-1.187	Destabilizing	None	N	0.147	neutral	N	0.457697258	None	None	N
T/C	0.2778	likely_benign	0.2474	benign	-0.887	Destabilizing	0.676	D	0.568	neutral	None	None	None	None	N
T/D	0.4198	ambiguous	0.3949	ambiguous	-1.309	Destabilizing	0.016	N	0.508	neutral	None	None	None	None	N
T/E	0.2621	likely_benign	0.2554	benign	-1.136	Destabilizing	None	N	0.297	neutral	None	None	None	None	N
T/F	0.2011	likely_benign	0.1806	benign	-0.959	Destabilizing	0.356	N	0.591	neutral	None	None	None	None	N
T/G	0.2435	likely_benign	0.2173	benign	-1.579	Destabilizing	0.016	N	0.513	neutral	None	None	None	None	N
T/H	0.2263	likely_benign	0.2139	benign	-1.737	Destabilizing	0.356	N	0.589	neutral	None	None	None	None	N
T/I	0.1128	likely_benign	0.1039	benign	-0.17	Destabilizing	0.055	N	0.601	neutral	N	0.457684031	None	None	N
T/K	0.1876	likely_benign	0.1896	benign	-0.537	Destabilizing	None	N	0.299	neutral	None	None	None	None	N
T/L	0.089	likely_benign	0.0874	benign	-0.17	Destabilizing	0.031	N	0.511	neutral	None	None	None	None	N
T/M	0.0792	likely_benign	0.0775	benign	-0.138	Destabilizing	0.356	N	0.581	neutral	None	None	None	None	N
T/N	0.1434	likely_benign	0.1332	benign	-1.126	Destabilizing	0.029	N	0.464	neutral	N	0.498211409	None	None	N
T/P	0.667	likely_pathogenic	0.6754	pathogenic	-0.478	Destabilizing	0.055	N	0.575	neutral	N	0.505048264	None	None	N
T/Q	0.2003	likely_benign	0.1926	benign	-0.986	Destabilizing	0.001	N	0.4	neutral	None	None	None	None	N
T/R	0.1363	likely_benign	0.141	benign	-0.686	Destabilizing	0.038	N	0.547	neutral	None	None	None	None	N
T/S	0.1007	likely_benign	0.0911	benign	-1.373	Destabilizing	None	N	0.195	neutral	N	0.4893424	None	None	N
T/V	0.0962	likely_benign	0.0921	benign	-0.478	Destabilizing	0.016	N	0.432	neutral	None	None	None	None	N
T/W	0.5406	ambiguous	0.5	ambiguous	-1.047	Destabilizing	0.864	D	0.609	neutral	None	None	None	None	N
T/Y	0.2489	likely_benign	0.2258	benign	-0.682	Destabilizing	0.356	N	0.589	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.