TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14580	43963;43964;43965	chr2:178632156;178632155;178632154	chr2:179496883;179496882;179496881
N2AB	12939	39040;39041;39042	chr2:178632156;178632155;178632154	chr2:179496883;179496882;179496881
N2A	12012	36259;36260;36261	chr2:178632156;178632155;178632154	chr2:179496883;179496882;179496881
N2B	5515	16768;16769;16770	chr2:178632156;178632155;178632154	chr2:179496883;179496882;179496881
Novex-1	5640	17143;17144;17145	chr2:178632156;178632155;178632154	chr2:179496883;179496882;179496881
Novex-2	5707	17344;17345;17346	chr2:178632156;178632155;178632154	chr2:179496883;179496882;179496881
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-96
• Domain position: 84
• Structural Position: 175
• Q(SASA): 0.3757
• 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	rs1381530830	-0.828	0.958	D	0.499	0.667	0.4744847356	gnomAD-2.1.1	4.34E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	9.52E-06	0
T/I	None	None	0.142	D	0.254	0.402	0.478299402934	gnomAD-4.0.0	1.64042E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.93719E-06	0	0
T/S	None	None	0.979	D	0.506	0.593	0.381239546501	gnomAD-4.0.0	1.64042E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.93719E-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	0.1586	likely_benign	0.1384	benign	-0.931	Destabilizing	0.958	D	0.499	neutral	D	0.638976866	None	None	N
T/C	0.6815	likely_pathogenic	0.6639	pathogenic	-0.653	Destabilizing	1.0	D	0.692	prob.neutral	None	None	None	None	N
T/D	0.5415	ambiguous	0.4383	ambiguous	-0.505	Destabilizing	0.998	D	0.713	prob.delet.	None	None	None	None	N
T/E	0.3949	ambiguous	0.3241	benign	-0.483	Destabilizing	0.998	D	0.713	prob.delet.	None	None	None	None	N
T/F	0.3165	likely_benign	0.259	benign	-0.916	Destabilizing	0.991	D	0.717	prob.delet.	None	None	None	None	N
T/G	0.6223	likely_pathogenic	0.5597	ambiguous	-1.21	Destabilizing	0.995	D	0.667	neutral	None	None	None	None	N
T/H	0.2974	likely_benign	0.2584	benign	-1.449	Destabilizing	1.0	D	0.711	prob.delet.	None	None	None	None	N
T/I	0.1838	likely_benign	0.1329	benign	-0.268	Destabilizing	0.142	N	0.254	neutral	D	0.585329789	None	None	N
T/K	0.2763	likely_benign	0.2325	benign	-0.825	Destabilizing	0.995	D	0.714	prob.delet.	None	None	None	None	N
T/L	0.1475	likely_benign	0.1224	benign	-0.268	Destabilizing	0.839	D	0.511	neutral	None	None	None	None	N
T/M	0.1034	likely_benign	0.1017	benign	0.026	Stabilizing	0.998	D	0.7	prob.neutral	None	None	None	None	N
T/N	0.1875	likely_benign	0.1425	benign	-0.857	Destabilizing	0.998	D	0.673	neutral	D	0.575811302	None	None	N
T/P	0.6679	likely_pathogenic	0.6693	pathogenic	-0.457	Destabilizing	0.998	D	0.71	prob.delet.	D	0.676393108	None	None	N
T/Q	0.2951	likely_benign	0.2728	benign	-1.023	Destabilizing	0.998	D	0.713	prob.delet.	None	None	None	None	N
T/R	0.1901	likely_benign	0.1824	benign	-0.586	Destabilizing	0.998	D	0.712	prob.delet.	None	None	None	None	N
T/S	0.2121	likely_benign	0.185	benign	-1.145	Destabilizing	0.979	D	0.506	neutral	D	0.618920845	None	None	N
T/V	0.1959	likely_benign	0.1593	benign	-0.457	Destabilizing	0.682	D	0.506	neutral	None	None	None	None	N
T/W	0.6867	likely_pathogenic	0.6364	pathogenic	-0.835	Destabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	N
T/Y	0.359	ambiguous	0.3178	benign	-0.602	Destabilizing	0.995	D	0.723	prob.delet.	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.