TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5033	15322;15323;15324	chr2:178734827;178734826;178734825	chr2:179599554;179599553;179599552
N2AB	4716	14371;14372;14373	chr2:178734827;178734826;178734825	chr2:179599554;179599553;179599552
N2A	3789	11590;11591;11592	chr2:178734827;178734826;178734825	chr2:179599554;179599553;179599552
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Ig-33
• Domain position: 53
• Structural Position: 130
• Q(SASA): 0.6652
• 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
V/I	rs1296327328	None	0.027	N	0.213	0.084	0.513787655203	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-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
V/A	0.099	likely_benign	0.114	benign	-0.579	Destabilizing	None	N	0.077	neutral	N	0.510046488	None	None	I
V/C	0.5686	likely_pathogenic	0.5882	pathogenic	-0.712	Destabilizing	0.824	D	0.261	neutral	None	None	None	None	I
V/D	0.15	likely_benign	0.159	benign	-0.085	Destabilizing	0.117	N	0.374	neutral	N	0.467020121	None	None	I
V/E	0.1356	likely_benign	0.1527	benign	-0.155	Destabilizing	0.149	N	0.324	neutral	None	None	None	None	I
V/F	0.1251	likely_benign	0.1371	benign	-0.555	Destabilizing	0.484	N	0.277	neutral	N	0.511373087	None	None	I
V/G	0.1406	likely_benign	0.1498	benign	-0.76	Destabilizing	0.062	N	0.333	neutral	N	0.507282568	None	None	I
V/H	0.2867	likely_benign	0.3143	benign	-0.18	Destabilizing	0.935	D	0.309	neutral	None	None	None	None	I
V/I	0.0704	likely_benign	0.0745	benign	-0.234	Destabilizing	0.027	N	0.213	neutral	N	0.492435847	None	None	I
V/K	0.1922	likely_benign	0.1975	benign	-0.492	Destabilizing	0.001	N	0.165	neutral	None	None	None	None	I
V/L	0.1263	likely_benign	0.1426	benign	-0.234	Destabilizing	0.027	N	0.249	neutral	N	0.495592617	None	None	I
V/M	0.1097	likely_benign	0.1234	benign	-0.431	Destabilizing	0.555	D	0.242	neutral	None	None	None	None	I
V/N	0.1131	likely_benign	0.1256	benign	-0.313	Destabilizing	0.38	N	0.373	neutral	None	None	None	None	I
V/P	0.5861	likely_pathogenic	0.6427	pathogenic	-0.313	Destabilizing	0.38	N	0.349	neutral	None	None	None	None	I
V/Q	0.1586	likely_benign	0.1716	benign	-0.478	Destabilizing	0.38	N	0.345	neutral	None	None	None	None	I
V/R	0.1774	likely_benign	0.1801	benign	-0.021	Destabilizing	0.081	N	0.351	neutral	None	None	None	None	I
V/S	0.1005	likely_benign	0.1086	benign	-0.757	Destabilizing	0.035	N	0.271	neutral	None	None	None	None	I
V/T	0.1109	likely_benign	0.1257	benign	-0.715	Destabilizing	0.001	N	0.146	neutral	None	None	None	None	I
V/W	0.6255	likely_pathogenic	0.6712	pathogenic	-0.649	Destabilizing	0.935	D	0.344	neutral	None	None	None	None	I
V/Y	0.3287	likely_benign	0.3614	ambiguous	-0.36	Destabilizing	0.555	D	0.275	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.