TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25706	77341;77342;77343	chr2:178569016;178569015;178569014	chr2:179433743;179433742;179433741
N2AB	24065	72418;72419;72420	chr2:178569016;178569015;178569014	chr2:179433743;179433742;179433741
N2A	23138	69637;69638;69639	chr2:178569016;178569015;178569014	chr2:179433743;179433742;179433741
N2B	16641	50146;50147;50148	chr2:178569016;178569015;178569014	chr2:179433743;179433742;179433741
Novex-1	16766	50521;50522;50523	chr2:178569016;178569015;178569014	chr2:179433743;179433742;179433741
Novex-2	16833	50722;50723;50724	chr2:178569016;178569015;178569014	chr2:179433743;179433742;179433741
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: Fn3-75
• Domain position: 9
• Structural Position: 11
• Q(SASA): 0.4112
• 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	rs1707111978	None	0.001	N	0.152	0.116	0.132336055621	gnomAD-4.0.0	1.59225E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	0	3.02645E-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	0.1049	likely_benign	0.09	benign	-0.82	Destabilizing	0.001	N	0.152	neutral	N	0.515942716	None	None	I
T/C	0.4636	ambiguous	0.4248	ambiguous	-0.542	Destabilizing	0.993	D	0.565	neutral	None	None	None	None	I
T/D	0.5356	ambiguous	0.4835	ambiguous	0.21	Stabilizing	0.339	N	0.526	neutral	None	None	None	None	I
T/E	0.4343	ambiguous	0.3808	ambiguous	0.228	Stabilizing	0.63	D	0.495	neutral	None	None	None	None	I
T/F	0.2856	likely_benign	0.2383	benign	-0.998	Destabilizing	0.957	D	0.625	neutral	None	None	None	None	I
T/G	0.3228	likely_benign	0.2892	benign	-1.074	Destabilizing	0.682	D	0.532	neutral	None	None	None	None	I
T/H	0.3248	likely_benign	0.2872	benign	-1.34	Destabilizing	0.995	D	0.598	neutral	None	None	None	None	I
T/I	0.1759	likely_benign	0.1371	benign	-0.236	Destabilizing	0.006	N	0.323	neutral	N	0.469473135	None	None	I
T/K	0.3363	likely_benign	0.2797	benign	-0.503	Destabilizing	0.705	D	0.524	neutral	None	None	None	None	I
T/L	0.1312	likely_benign	0.1081	benign	-0.236	Destabilizing	0.145	N	0.461	neutral	None	None	None	None	I
T/M	0.0963	likely_benign	0.0836	benign	-0.066	Destabilizing	0.893	D	0.579	neutral	None	None	None	None	I
T/N	0.1795	likely_benign	0.1542	benign	-0.552	Destabilizing	0.279	N	0.462	neutral	N	0.494124649	None	None	I
T/P	0.7256	likely_pathogenic	0.6622	pathogenic	-0.398	Destabilizing	0.733	D	0.592	neutral	N	0.489401042	None	None	I
T/Q	0.3172	likely_benign	0.2847	benign	-0.622	Destabilizing	0.797	D	0.588	neutral	None	None	None	None	I
T/R	0.2798	likely_benign	0.2367	benign	-0.389	Destabilizing	0.957	D	0.595	neutral	None	None	None	None	I
T/S	0.1275	likely_benign	0.1144	benign	-0.886	Destabilizing	0.001	N	0.143	neutral	N	0.45489147	None	None	I
T/V	0.1342	likely_benign	0.1136	benign	-0.398	Destabilizing	0.108	N	0.445	neutral	None	None	None	None	I
T/W	0.6642	likely_pathogenic	0.6248	pathogenic	-0.944	Destabilizing	0.998	D	0.639	neutral	None	None	None	None	I
T/Y	0.3712	ambiguous	0.3314	benign	-0.678	Destabilizing	0.978	D	0.625	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.