TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32220	96883;96884;96885	chr2:178543315;178543314;178543313	chr2:179408042;179408041;179408040
N2AB	30579	91960;91961;91962	chr2:178543315;178543314;178543313	chr2:179408042;179408041;179408040
N2A	29652	89179;89180;89181	chr2:178543315;178543314;178543313	chr2:179408042;179408041;179408040
N2B	23155	69688;69689;69690	chr2:178543315;178543314;178543313	chr2:179408042;179408041;179408040
Novex-1	23280	70063;70064;70065	chr2:178543315;178543314;178543313	chr2:179408042;179408041;179408040
Novex-2	23347	70264;70265;70266	chr2:178543315;178543314;178543313	chr2:179408042;179408041;179408040
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: Fn3-123
• Domain position: 19
• Structural Position: 21
• Q(SASA): 0.1433
• 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	rs727505204	0.116	0.031	N	0.379	0.173	0.303453137403	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.88E-06	0
T/I	rs727505204	0.116	0.031	N	0.379	0.173	0.303453137403	gnomAD-4.0.0	3.42088E-06	None	None	None	None	N	None	2.98793E-05	0	None	0	0	None	0	0	3.59778E-06	0	0
T/S	None	None	0.003	N	0.298	0.103	0.18995819373	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	0.1169	likely_benign	0.1016	benign	-1.013	Destabilizing	0.174	N	0.489	neutral	N	0.47085226	None	None	N
T/C	0.4127	ambiguous	0.3416	ambiguous	-1.004	Destabilizing	0.973	D	0.681	prob.neutral	None	None	None	None	N
T/D	0.5974	likely_pathogenic	0.5577	ambiguous	-1.552	Destabilizing	0.826	D	0.621	neutral	None	None	None	None	N
T/E	0.5303	ambiguous	0.4784	ambiguous	-1.436	Destabilizing	0.704	D	0.627	neutral	None	None	None	None	N
T/F	0.3467	ambiguous	0.2741	benign	-0.751	Destabilizing	0.906	D	0.732	prob.delet.	None	None	None	None	N
T/G	0.3067	likely_benign	0.248	benign	-1.358	Destabilizing	0.404	N	0.615	neutral	None	None	None	None	N
T/H	0.2707	likely_benign	0.2488	benign	-1.564	Destabilizing	0.973	D	0.729	prob.delet.	None	None	None	None	N
T/I	0.2056	likely_benign	0.1753	benign	-0.144	Destabilizing	0.031	N	0.379	neutral	N	0.470447413	None	None	N
T/K	0.2449	likely_benign	0.2383	benign	-0.937	Destabilizing	0.704	D	0.626	neutral	None	None	None	None	N
T/L	0.1441	likely_benign	0.1173	benign	-0.144	Destabilizing	0.404	N	0.539	neutral	None	None	None	None	N
T/M	0.1184	likely_benign	0.1058	benign	-0.114	Destabilizing	0.973	D	0.683	prob.neutral	None	None	None	None	N
T/N	0.1898	likely_benign	0.1726	benign	-1.351	Destabilizing	0.642	D	0.577	neutral	N	0.46913074	None	None	N
T/P	0.7248	likely_pathogenic	0.6202	pathogenic	-0.402	Destabilizing	0.782	D	0.675	neutral	N	0.500263595	None	None	N
T/Q	0.2768	likely_benign	0.2556	benign	-1.34	Destabilizing	0.826	D	0.705	prob.neutral	None	None	None	None	N
T/R	0.2007	likely_benign	0.195	benign	-0.878	Destabilizing	0.826	D	0.683	prob.neutral	None	None	None	None	N
T/S	0.1113	likely_benign	0.094	benign	-1.502	Destabilizing	0.003	N	0.298	neutral	N	0.478461763	None	None	N
T/V	0.1614	likely_benign	0.1407	benign	-0.402	Destabilizing	0.404	N	0.518	neutral	None	None	None	None	N
T/W	0.6667	likely_pathogenic	0.5674	pathogenic	-0.841	Destabilizing	0.991	D	0.712	prob.delet.	None	None	None	None	N
T/Y	0.3628	ambiguous	0.2926	benign	-0.517	Destabilizing	0.906	D	0.744	deleterious	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.