TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3995	12208;12209;12210	chr2:178741250;178741249;178741248	chr2:179605977;179605976;179605975
N2AB	3678	11257;11258;11259	chr2:178741250;178741249;178741248	chr2:179605977;179605976;179605975
N2A	None	None	chr2:None	chr2:None
N2B	3632	11119;11120;11121	chr2:178741250;178741249;178741248	chr2:179605977;179605976;179605975
Novex-1	3757	11494;11495;11496	chr2:178741250;178741249;178741248	chr2:179605977;179605976;179605975
Novex-2	3824	11695;11696;11697	chr2:178741250;178741249;178741248	chr2:179605977;179605976;179605975
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: Ig-28
• Domain position: 58
• Structural Position: 137
• Q(SASA): 0.1238
• 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/A	None	None	0.011	D	0.393	0.189	None	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
T/I	rs749320093	0.069	0.002	D	0.405	0.141	None	gnomAD-2.1.1	1.21E-05	None	None	None	None	N	None	6.48E-05	0	None	0	0	None	0	None	0	1.78E-05	0
T/I	rs749320093	0.069	0.002	D	0.405	0.141	None	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
T/I	rs749320093	0.069	0.002	D	0.405	0.141	None	gnomAD-4.0.0	6.81721E-06	None	None	None	None	N	None	2.6698E-05	0	None	0	0	None	0	0	7.6282E-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	0.107	likely_benign	0.1038	benign	-1.233	Destabilizing	0.011	N	0.393	neutral	D	0.547977668	None	None	N
T/C	0.4298	ambiguous	0.4172	ambiguous	-0.83	Destabilizing	0.001	N	0.522	neutral	None	None	None	None	N
T/D	0.5203	ambiguous	0.5009	ambiguous	-1.285	Destabilizing	0.033	N	0.594	neutral	None	None	None	None	N
T/E	0.381	ambiguous	0.384	ambiguous	-1.075	Destabilizing	0.033	N	0.582	neutral	None	None	None	None	N
T/F	0.2791	likely_benign	0.2712	benign	-0.812	Destabilizing	0.001	N	0.502	neutral	None	None	None	None	N
T/G	0.4271	ambiguous	0.4091	ambiguous	-1.651	Destabilizing	0.033	N	0.613	neutral	None	None	None	None	N
T/H	0.2813	likely_benign	0.2878	benign	-1.628	Destabilizing	0.54	D	0.636	neutral	None	None	None	None	N
T/I	0.1658	likely_benign	0.169	benign	-0.129	Destabilizing	0.002	N	0.405	neutral	D	0.5537281	None	None	N
T/K	0.1738	likely_benign	0.2177	benign	-0.461	Destabilizing	None	N	0.401	neutral	None	None	None	None	N
T/L	0.1282	likely_benign	0.131	benign	-0.129	Destabilizing	None	N	0.357	neutral	None	None	None	None	N
T/M	0.1032	likely_benign	0.1054	benign	-0.244	Destabilizing	0.367	N	0.651	neutral	None	None	None	None	N
T/N	0.1768	likely_benign	0.1664	benign	-1.115	Destabilizing	None	N	0.225	neutral	D	0.545527773	None	None	N
T/P	0.6472	likely_pathogenic	0.6414	pathogenic	-0.466	Destabilizing	None	N	0.405	neutral	D	0.736981276	None	None	N
T/Q	0.2367	likely_benign	0.2658	benign	-0.887	Destabilizing	0.076	N	0.653	neutral	None	None	None	None	N
T/R	0.1384	likely_benign	0.1654	benign	-0.667	Destabilizing	0.001	N	0.409	neutral	None	None	None	None	N
T/S	0.1481	likely_benign	0.1396	benign	-1.391	Destabilizing	None	N	0.214	neutral	N	0.511878888	None	None	N
T/V	0.1689	likely_benign	0.1717	benign	-0.466	Destabilizing	0.015	N	0.384	neutral	None	None	None	None	N
T/W	0.6336	likely_pathogenic	0.6405	pathogenic	-0.92	Destabilizing	0.931	D	0.643	neutral	None	None	None	None	N
T/Y	0.2853	likely_benign	0.2811	benign	-0.549	Destabilizing	0.076	N	0.659	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.