TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1165	3718;3719;3720	chr2:178781151;178781150;178781149	chr2:179645878;179645877;179645876
N2AB	1165	3718;3719;3720	chr2:178781151;178781150;178781149	chr2:179645878;179645877;179645876
N2A	1165	3718;3719;3720	chr2:178781151;178781150;178781149	chr2:179645878;179645877;179645876
N2B	1119	3580;3581;3582	chr2:178781151;178781150;178781149	chr2:179645878;179645877;179645876
Novex-1	1119	3580;3581;3582	chr2:178781151;178781150;178781149	chr2:179645878;179645877;179645876
Novex-2	1119	3580;3581;3582	chr2:178781151;178781150;178781149	chr2:179645878;179645877;179645876
Novex-3	1165	3718;3719;3720	chr2:178781151;178781150;178781149	chr2:179645878;179645877;179645876

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Ig-4
• Domain position: 84
• Structural Position: 166
• Q(SASA): 0.1887
• 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
T/I	None	None	None	N	0.253	0.096	0.144782658237	gnomAD-4.0.0	1.59087E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85701E-06	0	0
T/N	rs762456074	-0.58	0.484	N	0.51	0.105	0.21737058555	gnomAD-2.1.1	3.98E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.82E-06	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	0.0786	likely_benign	0.0783	benign	-0.836	Destabilizing	None	N	0.103	neutral	N	0.323625348	None	None	I
T/C	0.45	ambiguous	0.4461	ambiguous	-0.538	Destabilizing	0.791	D	0.507	neutral	None	None	None	None	I
T/D	0.5508	ambiguous	0.574	pathogenic	-0.032	Destabilizing	0.262	N	0.537	neutral	None	None	None	None	I
T/E	0.4338	ambiguous	0.4478	ambiguous	0.018	Stabilizing	0.149	N	0.544	neutral	None	None	None	None	I
T/F	0.2712	likely_benign	0.2856	benign	-0.79	Destabilizing	0.38	N	0.613	neutral	None	None	None	None	I
T/G	0.3774	ambiguous	0.4015	ambiguous	-1.132	Destabilizing	0.081	N	0.582	neutral	None	None	None	None	I
T/H	0.3966	ambiguous	0.4185	ambiguous	-1.27	Destabilizing	0.935	D	0.575	neutral	None	None	None	None	I
T/I	0.1028	likely_benign	0.1005	benign	-0.125	Destabilizing	None	N	0.253	neutral	N	0.431331284	None	None	I
T/K	0.3351	likely_benign	0.3474	ambiguous	-0.52	Destabilizing	0.149	N	0.542	neutral	None	None	None	None	I
T/L	0.1072	likely_benign	0.1052	benign	-0.125	Destabilizing	0.012	N	0.455	neutral	None	None	None	None	I
T/M	0.0889	likely_benign	0.0886	benign	-0.107	Destabilizing	0.38	N	0.516	neutral	None	None	None	None	I
T/N	0.1752	likely_benign	0.1953	benign	-0.624	Destabilizing	0.484	N	0.51	neutral	N	0.486100735	None	None	I
T/P	0.8874	likely_pathogenic	0.9081	pathogenic	-0.329	Destabilizing	0.484	N	0.534	neutral	N	0.511578919	None	None	I
T/Q	0.3287	likely_benign	0.3447	ambiguous	-0.663	Destabilizing	0.555	D	0.531	neutral	None	None	None	None	I
T/R	0.2835	likely_benign	0.3021	benign	-0.388	Destabilizing	0.555	D	0.538	neutral	None	None	None	None	I
T/S	0.1425	likely_benign	0.1502	benign	-0.941	Destabilizing	0.027	N	0.445	neutral	N	0.444151541	None	None	I
T/V	0.1004	likely_benign	0.0959	benign	-0.329	Destabilizing	None	N	0.091	neutral	None	None	None	None	I
T/W	0.7647	likely_pathogenic	0.7701	pathogenic	-0.756	Destabilizing	0.935	D	0.612	neutral	None	None	None	None	I
T/Y	0.3935	ambiguous	0.4039	ambiguous	-0.484	Destabilizing	0.555	D	0.611	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.