TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3902	11929;11930;11931	chr2:178741529;178741528;178741527	chr2:179606256;179606255;179606254
N2AB	3585	10978;10979;10980	chr2:178741529;178741528;178741527	chr2:179606256;179606255;179606254
N2A	None	None	chr2:None	chr2:None
N2B	3539	10840;10841;10842	chr2:178741529;178741528;178741527	chr2:179606256;179606255;179606254
Novex-1	3664	11215;11216;11217	chr2:178741529;178741528;178741527	chr2:179606256;179606255;179606254
Novex-2	3731	11416;11417;11418	chr2:178741529;178741528;178741527	chr2:179606256;179606255;179606254
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATA
• RefSeq wild type template codon: TAT
• Domain: Ig-27
• Domain position: 83
• Structural Position: 168
• Q(SASA): 0.617
• 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
I/M	rs368845723	-0.233	None	N	0.205	0.105	None	gnomAD-2.1.1	3.18E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	6.48E-05	0
I/M	rs368845723	-0.233	None	N	0.205	0.105	None	gnomAD-3.1.2	1.31E-05	None	None	None	None	I	None	0	0	0	0	0	None	0	0	2.94E-05	0	0
I/M	rs368845723	-0.233	None	N	0.205	0.105	None	gnomAD-4.0.0	4.95726E-06	None	None	None	None	I	None	4.00299E-05	0	None	0	0	None	0	0	4.23791E-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
I/A	0.1666	likely_benign	0.1349	benign	-1.257	Destabilizing	None	N	0.208	neutral	None	None	None	None	I
I/C	0.5126	ambiguous	0.4699	ambiguous	-0.592	Destabilizing	0.132	N	0.453	neutral	None	None	None	None	I
I/D	0.426	ambiguous	0.3508	ambiguous	-0.612	Destabilizing	0.009	N	0.353	neutral	None	None	None	None	I
I/E	0.3088	likely_benign	0.2593	benign	-0.658	Destabilizing	0.002	N	0.363	neutral	None	None	None	None	I
I/F	0.1258	likely_benign	0.1082	benign	-1.0	Destabilizing	0.021	N	0.431	neutral	None	None	None	None	I
I/G	0.429	ambiguous	0.355	ambiguous	-1.518	Destabilizing	None	N	0.378	neutral	None	None	None	None	I
I/H	0.314	likely_benign	0.2777	benign	-0.716	Destabilizing	0.132	N	0.507	neutral	None	None	None	None	I
I/K	0.1989	likely_benign	0.1748	benign	-0.712	Destabilizing	0.001	N	0.365	neutral	N	0.441381949	None	None	I
I/L	0.1072	likely_benign	0.0955	benign	-0.647	Destabilizing	None	N	0.185	neutral	N	0.450821427	None	None	I
I/M	0.091	likely_benign	0.0815	benign	-0.442	Destabilizing	None	N	0.205	neutral	N	0.485866674	None	None	I
I/N	0.1426	likely_benign	0.1241	benign	-0.419	Destabilizing	0.009	N	0.361	neutral	None	None	None	None	I
I/P	0.688	likely_pathogenic	0.5916	pathogenic	-0.818	Destabilizing	0.018	N	0.406	neutral	None	None	None	None	I
I/Q	0.2595	likely_benign	0.229	benign	-0.641	Destabilizing	None	N	0.418	neutral	None	None	None	None	I
I/R	0.142	likely_benign	0.1228	benign	-0.098	Destabilizing	None	N	0.415	neutral	N	0.383227261	None	None	I
I/S	0.1362	likely_benign	0.1159	benign	-0.965	Destabilizing	None	N	0.316	neutral	None	None	None	None	I
I/T	0.0909	likely_benign	0.0773	benign	-0.897	Destabilizing	None	N	0.199	neutral	N	0.361178016	None	None	I
I/V	0.0668	likely_benign	0.0636	benign	-0.818	Destabilizing	None	N	0.103	neutral	N	0.444503174	None	None	I
I/W	0.6463	likely_pathogenic	0.606	pathogenic	-1.027	Destabilizing	0.316	N	0.427	neutral	None	None	None	None	I
I/Y	0.3412	ambiguous	0.3137	benign	-0.803	Destabilizing	0.041	N	0.504	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.