TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28397	85414;85415;85416	chr2:178560943;178560942;178560941	chr2:179425670;179425669;179425668
N2AB	26756	80491;80492;80493	chr2:178560943;178560942;178560941	chr2:179425670;179425669;179425668
N2A	25829	77710;77711;77712	chr2:178560943;178560942;178560941	chr2:179425670;179425669;179425668
N2B	19332	58219;58220;58221	chr2:178560943;178560942;178560941	chr2:179425670;179425669;179425668
Novex-1	19457	58594;58595;58596	chr2:178560943;178560942;178560941	chr2:179425670;179425669;179425668
Novex-2	19524	58795;58796;58797	chr2:178560943;178560942;178560941	chr2:179425670;179425669;179425668
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: Ig-143
• Domain position: 40
• Structural Position: 56
• Q(SASA): 0.7723
• 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
E/D	None	None	0.999	N	0.511	0.215	0.297375071883	gnomAD-4.0.0	1.36841E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79889E-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	0.1337	likely_benign	0.1304	benign	-0.282	Destabilizing	0.999	D	0.67	neutral	N	0.499646436	None	None	N
E/C	0.7556	likely_pathogenic	0.7435	pathogenic	-0.063	Destabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	N
E/D	0.1256	likely_benign	0.1022	benign	-0.36	Destabilizing	0.999	D	0.511	neutral	N	0.511374763	None	None	N
E/F	0.6533	likely_pathogenic	0.6247	pathogenic	-0.148	Destabilizing	1.0	D	0.685	prob.neutral	None	None	None	None	N
E/G	0.2014	likely_benign	0.1798	benign	-0.472	Destabilizing	1.0	D	0.64	neutral	D	0.526108483	None	None	N
E/H	0.3929	ambiguous	0.373	ambiguous	0.151	Stabilizing	1.0	D	0.651	neutral	None	None	None	None	N
E/I	0.22	likely_benign	0.2203	benign	0.181	Stabilizing	1.0	D	0.699	prob.neutral	None	None	None	None	N
E/K	0.1441	likely_benign	0.1391	benign	0.414	Stabilizing	0.999	D	0.641	neutral	N	0.488579619	None	None	N
E/L	0.2708	likely_benign	0.2649	benign	0.181	Stabilizing	1.0	D	0.704	prob.neutral	None	None	None	None	N
E/M	0.3253	likely_benign	0.3336	benign	0.174	Stabilizing	1.0	D	0.657	neutral	None	None	None	None	N
E/N	0.229	likely_benign	0.1969	benign	0.028	Stabilizing	1.0	D	0.697	prob.neutral	None	None	None	None	N
E/P	0.3105	likely_benign	0.3008	benign	0.047	Stabilizing	1.0	D	0.694	prob.neutral	None	None	None	None	N
E/Q	0.1322	likely_benign	0.1346	benign	0.07	Stabilizing	1.0	D	0.605	neutral	N	0.501203372	None	None	N
E/R	0.2414	likely_benign	0.2357	benign	0.619	Stabilizing	1.0	D	0.691	prob.neutral	None	None	None	None	N
E/S	0.2038	likely_benign	0.1864	benign	-0.098	Destabilizing	0.999	D	0.654	neutral	None	None	None	None	N
E/T	0.1777	likely_benign	0.1729	benign	0.062	Stabilizing	1.0	D	0.702	prob.neutral	None	None	None	None	N
E/V	0.1351	likely_benign	0.1348	benign	0.047	Stabilizing	1.0	D	0.691	prob.neutral	D	0.529904596	None	None	N
E/W	0.8442	likely_pathogenic	0.8255	pathogenic	-0.005	Destabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	N
E/Y	0.5417	ambiguous	0.5004	ambiguous	0.099	Stabilizing	1.0	D	0.667	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.