TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2224	6895;6896;6897	chr2:178775041;178775040;178775039	chr2:179639768;179639767;179639766
N2AB	2224	6895;6896;6897	chr2:178775041;178775040;178775039	chr2:179639768;179639767;179639766
N2A	2224	6895;6896;6897	chr2:178775041;178775040;178775039	chr2:179639768;179639767;179639766
N2B	2178	6757;6758;6759	chr2:178775041;178775040;178775039	chr2:179639768;179639767;179639766
Novex-1	2178	6757;6758;6759	chr2:178775041;178775040;178775039	chr2:179639768;179639767;179639766
Novex-2	2178	6757;6758;6759	chr2:178775041;178775040;178775039	chr2:179639768;179639767;179639766
Novex-3	2224	6895;6896;6897	chr2:178775041;178775040;178775039	chr2:179639768;179639767;179639766

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCT
• RefSeq wild type template codon: AGA
• Domain: Ig-11
• Domain position: 51
• Structural Position: 127
• Q(SASA): 0.3291
• 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
S/C	None	None	1.0	D	0.769	0.508	0.609419018514	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	6.33473E-05	0	None	0	0	None	0	0	0	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
S/A	0.1179	likely_benign	0.1138	benign	-0.742	Destabilizing	0.997	D	0.587	neutral	N	0.484521304	None	None	N
S/C	0.213	likely_benign	0.209	benign	-0.31	Destabilizing	1.0	D	0.769	deleterious	D	0.568541801	None	None	N
S/D	0.78	likely_pathogenic	0.7862	pathogenic	-0.534	Destabilizing	0.999	D	0.719	prob.delet.	None	None	None	None	N
S/E	0.8132	likely_pathogenic	0.8194	pathogenic	-0.518	Destabilizing	0.999	D	0.708	prob.delet.	None	None	None	None	N
S/F	0.4033	ambiguous	0.3959	ambiguous	-0.826	Destabilizing	1.0	D	0.819	deleterious	N	0.503744805	None	None	N
S/G	0.1834	likely_benign	0.1821	benign	-1.022	Destabilizing	0.999	D	0.674	neutral	None	None	None	None	N
S/H	0.5505	ambiguous	0.5623	ambiguous	-1.531	Destabilizing	1.0	D	0.784	deleterious	None	None	None	None	N
S/I	0.3982	ambiguous	0.3894	ambiguous	-0.093	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
S/K	0.8682	likely_pathogenic	0.8736	pathogenic	-0.857	Destabilizing	0.999	D	0.712	prob.delet.	None	None	None	None	N
S/L	0.2158	likely_benign	0.2118	benign	-0.093	Destabilizing	1.0	D	0.734	prob.delet.	None	None	None	None	N
S/M	0.3484	ambiguous	0.34	benign	0.229	Stabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
S/N	0.3362	likely_benign	0.3448	ambiguous	-0.818	Destabilizing	0.999	D	0.713	prob.delet.	None	None	None	None	N
S/P	0.8964	likely_pathogenic	0.8934	pathogenic	-0.274	Destabilizing	1.0	D	0.784	deleterious	N	0.506032827	None	None	N
S/Q	0.6851	likely_pathogenic	0.6928	pathogenic	-0.889	Destabilizing	1.0	D	0.767	deleterious	None	None	None	None	N
S/R	0.7636	likely_pathogenic	0.771	pathogenic	-0.788	Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	N
S/T	0.111	likely_benign	0.1105	benign	-0.744	Destabilizing	0.999	D	0.69	prob.neutral	N	0.49896564	None	None	N
S/V	0.3388	likely_benign	0.3308	benign	-0.274	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
S/W	0.5882	likely_pathogenic	0.583	pathogenic	-0.885	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
S/Y	0.3757	ambiguous	0.3672	ambiguous	-0.624	Destabilizing	1.0	D	0.819	deleterious	N	0.507163489	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.