TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25031	75316;75317;75318	chr2:178571041;178571040;178571039	chr2:179435768;179435767;179435766
N2AB	23390	70393;70394;70395	chr2:178571041;178571040;178571039	chr2:179435768;179435767;179435766
N2A	22463	67612;67613;67614	chr2:178571041;178571040;178571039	chr2:179435768;179435767;179435766
N2B	15966	48121;48122;48123	chr2:178571041;178571040;178571039	chr2:179435768;179435767;179435766
Novex-1	16091	48496;48497;48498	chr2:178571041;178571040;178571039	chr2:179435768;179435767;179435766
Novex-2	16158	48697;48698;48699	chr2:178571041;178571040;178571039	chr2:179435768;179435767;179435766
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: Fn3-70
• Domain position: 26
• Structural Position: 28
• Q(SASA): 0.971
• 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	rs756363402	0.126	None	N	0.129	0.105	0.180583059064	gnomAD-4.0.0	3.60097E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.93751E-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	0.0529	likely_benign	0.0542	benign	-0.301	Destabilizing	None	N	0.052	neutral	N	0.378028197	None	None	N
T/C	0.2803	likely_benign	0.2917	benign	-0.238	Destabilizing	0.245	N	0.223	neutral	None	None	None	None	N
T/D	0.1867	likely_benign	0.1965	benign	0.089	Stabilizing	0.009	N	0.229	neutral	None	None	None	None	N
T/E	0.1216	likely_benign	0.1252	benign	0.002	Stabilizing	None	N	0.103	neutral	None	None	None	None	N
T/F	0.1536	likely_benign	0.1674	benign	-0.843	Destabilizing	0.044	N	0.34	neutral	None	None	None	None	N
T/G	0.1364	likely_benign	0.1426	benign	-0.41	Destabilizing	0.009	N	0.203	neutral	None	None	None	None	N
T/H	0.1881	likely_benign	0.1987	benign	-0.686	Destabilizing	0.245	N	0.266	neutral	None	None	None	None	N
T/I	0.0735	likely_benign	0.0808	benign	-0.137	Destabilizing	None	N	0.129	neutral	N	0.404081435	None	None	N
T/K	0.1362	likely_benign	0.1366	benign	-0.352	Destabilizing	0.009	N	0.215	neutral	None	None	None	None	N
T/L	0.0594	likely_benign	0.0616	benign	-0.137	Destabilizing	None	N	0.1	neutral	None	None	None	None	N
T/M	0.0716	likely_benign	0.0749	benign	0.005	Stabilizing	0.138	N	0.227	neutral	None	None	None	None	N
T/N	0.0786	likely_benign	0.0813	benign	-0.1	Destabilizing	0.033	N	0.207	neutral	N	0.445773342	None	None	N
T/P	0.0991	likely_benign	0.0945	benign	-0.164	Destabilizing	0.033	N	0.326	neutral	N	0.424531278	None	None	N
T/Q	0.1317	likely_benign	0.1342	benign	-0.343	Destabilizing	0.002	N	0.179	neutral	None	None	None	None	N
T/R	0.1318	likely_benign	0.1287	benign	-0.058	Destabilizing	0.044	N	0.345	neutral	None	None	None	None	N
T/S	0.0754	likely_benign	0.0774	benign	-0.288	Destabilizing	0.003	N	0.113	neutral	N	0.406753593	None	None	N
T/V	0.0658	likely_benign	0.0699	benign	-0.164	Destabilizing	None	N	0.073	neutral	None	None	None	None	N
T/W	0.4838	ambiguous	0.4981	ambiguous	-0.87	Destabilizing	0.788	D	0.245	neutral	None	None	None	None	N
T/Y	0.2036	likely_benign	0.2065	benign	-0.579	Destabilizing	0.245	N	0.346	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.