TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30012	90259;90260;90261	chr2:178552866;178552865;178552864	chr2:179417593;179417592;179417591
N2AB	28371	85336;85337;85338	chr2:178552866;178552865;178552864	chr2:179417593;179417592;179417591
N2A	27444	82555;82556;82557	chr2:178552866;178552865;178552864	chr2:179417593;179417592;179417591
N2B	20947	63064;63065;63066	chr2:178552866;178552865;178552864	chr2:179417593;179417592;179417591
Novex-1	21072	63439;63440;63441	chr2:178552866;178552865;178552864	chr2:179417593;179417592;179417591
Novex-2	21139	63640;63641;63642	chr2:178552866;178552865;178552864	chr2:179417593;179417592;179417591
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-106
• Domain position: 80
• Structural Position: 113
• Q(SASA): 0.7128
• 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
E/K	rs796978396	None	0.999	N	0.609	0.394	0.367803931526	gnomAD-4.0.0	3.4211E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	4.49726E-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
E/A	0.28	likely_benign	0.2495	benign	-0.492	Destabilizing	0.999	D	0.606	neutral	N	0.512360906	None	None	I
E/C	0.9436	likely_pathogenic	0.9347	pathogenic	-0.183	Destabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	I
E/D	0.2107	likely_benign	0.189	benign	-0.377	Destabilizing	0.999	D	0.419	neutral	D	0.523289976	None	None	I
E/F	0.9327	likely_pathogenic	0.9224	pathogenic	-0.274	Destabilizing	1.0	D	0.635	neutral	None	None	None	None	I
E/G	0.3254	likely_benign	0.2969	benign	-0.689	Destabilizing	1.0	D	0.575	neutral	N	0.482046165	None	None	I
E/H	0.6796	likely_pathogenic	0.6443	pathogenic	0.029	Stabilizing	1.0	D	0.655	neutral	None	None	None	None	I
E/I	0.5832	likely_pathogenic	0.5685	pathogenic	-0.003	Destabilizing	1.0	D	0.647	neutral	None	None	None	None	I
E/K	0.2161	likely_benign	0.1983	benign	0.276	Stabilizing	0.999	D	0.609	neutral	N	0.470052924	None	None	I
E/L	0.7067	likely_pathogenic	0.6862	pathogenic	-0.003	Destabilizing	1.0	D	0.624	neutral	None	None	None	None	I
E/M	0.7146	likely_pathogenic	0.6856	pathogenic	0.069	Stabilizing	1.0	D	0.637	neutral	None	None	None	None	I
E/N	0.4391	ambiguous	0.4099	ambiguous	-0.18	Destabilizing	1.0	D	0.691	prob.neutral	None	None	None	None	I
E/P	0.73	likely_pathogenic	0.7304	pathogenic	-0.147	Destabilizing	1.0	D	0.629	neutral	None	None	None	None	I
E/Q	0.2295	likely_benign	0.2111	benign	-0.12	Destabilizing	1.0	D	0.587	neutral	D	0.524002052	None	None	I
E/R	0.388	ambiguous	0.3716	ambiguous	0.516	Stabilizing	1.0	D	0.687	prob.neutral	None	None	None	None	I
E/S	0.3584	ambiguous	0.3373	benign	-0.306	Destabilizing	0.999	D	0.639	neutral	None	None	None	None	I
E/T	0.4195	ambiguous	0.3852	ambiguous	-0.134	Destabilizing	1.0	D	0.636	neutral	None	None	None	None	I
E/V	0.4081	ambiguous	0.3831	ambiguous	-0.147	Destabilizing	1.0	D	0.627	neutral	N	0.481902169	None	None	I
E/W	0.9778	likely_pathogenic	0.9742	pathogenic	-0.079	Destabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	I
E/Y	0.8455	likely_pathogenic	0.8276	pathogenic	-0.028	Destabilizing	1.0	D	0.641	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.