TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18407	55444;55445;55446	chr2:178602052;178602051;178602050	chr2:179466779;179466778;179466777
N2AB	16766	50521;50522;50523	chr2:178602052;178602051;178602050	chr2:179466779;179466778;179466777
N2A	15839	47740;47741;47742	chr2:178602052;178602051;178602050	chr2:179466779;179466778;179466777
N2B	9342	28249;28250;28251	chr2:178602052;178602051;178602050	chr2:179466779;179466778;179466777
Novex-1	9467	28624;28625;28626	chr2:178602052;178602051;178602050	chr2:179466779;179466778;179466777
Novex-2	9534	28825;28826;28827	chr2:178602052;178602051;178602050	chr2:179466779;179466778;179466777
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Ig-115
• Domain position: 26
• Structural Position: 43
• Q(SASA): 0.4433
• Predicted PPI site: I

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	0.022	N	0.122	0.132	0.206339911435	gnomAD-4.0.0	1.59329E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.86218E-06	0	0
T/I	None	None	0.669	N	0.317	0.183	0.341696514166	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	6.33473E-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
T/A	0.0606	likely_benign	0.0578	benign	-0.566	Destabilizing	0.022	N	0.122	neutral	N	0.427873519	None	None	I
T/C	0.3018	likely_benign	0.307	benign	-0.325	Destabilizing	0.998	D	0.409	neutral	None	None	None	None	I
T/D	0.3788	ambiguous	0.3423	ambiguous	0.014	Stabilizing	0.974	D	0.379	neutral	None	None	None	None	I
T/E	0.2362	likely_benign	0.2253	benign	-0.038	Destabilizing	0.915	D	0.371	neutral	None	None	None	None	I
T/F	0.1609	likely_benign	0.1509	benign	-0.813	Destabilizing	0.949	D	0.527	neutral	None	None	None	None	I
T/G	0.243	likely_benign	0.2276	benign	-0.756	Destabilizing	0.728	D	0.445	neutral	None	None	None	None	I
T/H	0.2131	likely_benign	0.2124	benign	-1.077	Destabilizing	0.998	D	0.513	neutral	None	None	None	None	I
T/I	0.073	likely_benign	0.0703	benign	-0.168	Destabilizing	0.669	D	0.317	neutral	N	0.49633074	None	None	I
T/K	0.1138	likely_benign	0.1371	benign	-0.651	Destabilizing	0.801	D	0.363	neutral	N	0.47539532	None	None	I
T/L	0.0605	likely_benign	0.0595	benign	-0.168	Destabilizing	0.525	D	0.354	neutral	None	None	None	None	I
T/M	0.0712	likely_benign	0.0694	benign	0.07	Stabilizing	0.974	D	0.415	neutral	None	None	None	None	I
T/N	0.1142	likely_benign	0.1076	benign	-0.379	Destabilizing	0.991	D	0.356	neutral	None	None	None	None	I
T/P	0.0803	likely_benign	0.0729	benign	-0.27	Destabilizing	0.966	D	0.398	neutral	N	0.460639298	None	None	I
T/Q	0.1495	likely_benign	0.1572	benign	-0.605	Destabilizing	0.991	D	0.427	neutral	None	None	None	None	I
T/R	0.1191	likely_benign	0.1383	benign	-0.38	Destabilizing	0.966	D	0.427	neutral	N	0.490519488	None	None	I
T/S	0.0996	likely_benign	0.0925	benign	-0.624	Destabilizing	0.454	N	0.315	neutral	N	0.501043126	None	None	I
T/V	0.0669	likely_benign	0.0664	benign	-0.27	Destabilizing	0.007	N	0.127	neutral	None	None	None	None	I
T/W	0.5241	ambiguous	0.5179	ambiguous	-0.768	Destabilizing	0.998	D	0.565	neutral	None	None	None	None	I
T/Y	0.2202	likely_benign	0.2026	benign	-0.54	Destabilizing	0.974	D	0.516	neutral	None	None	None	None	I

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.