TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3941	12046;12047;12048	chr2:178741412;178741411;178741410	chr2:179606139;179606138;179606137
N2AB	3624	11095;11096;11097	chr2:178741412;178741411;178741410	chr2:179606139;179606138;179606137
N2A	None	None	chr2:None	chr2:None
N2B	3578	10957;10958;10959	chr2:178741412;178741411;178741410	chr2:179606139;179606138;179606137
Novex-1	3703	11332;11333;11334	chr2:178741412;178741411;178741410	chr2:179606139;179606138;179606137
Novex-2	3770	11533;11534;11535	chr2:178741412;178741411;178741410	chr2:179606139;179606138;179606137
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Ig-28
• Domain position: 4
• Structural Position: 4
• Q(SASA): 0.9389
• 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
L/H	None	None	0.822	N	0.259	0.125	None	gnomAD-4.0.0	1.5911E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85791E-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
L/A	0.2188	likely_benign	0.2115	benign	-1.06	Destabilizing	None	N	0.127	neutral	None	None	None	None	I
L/C	0.331	likely_benign	0.3247	benign	-0.634	Destabilizing	0.667	D	0.273	neutral	None	None	None	None	I
L/D	0.543	ambiguous	0.5222	ambiguous	-0.68	Destabilizing	0.22	N	0.339	neutral	None	None	None	None	I
L/E	0.2307	likely_benign	0.2179	benign	-0.726	Destabilizing	0.22	N	0.332	neutral	None	None	None	None	I
L/F	0.1059	likely_benign	0.1055	benign	-0.79	Destabilizing	0.001	N	0.123	neutral	N	0.490745615	None	None	I
L/G	0.437	ambiguous	0.4233	ambiguous	-1.303	Destabilizing	0.055	N	0.244	neutral	None	None	None	None	I
L/H	0.156	likely_benign	0.154	benign	-0.481	Destabilizing	0.822	D	0.259	neutral	N	0.445563678	None	None	I
L/I	0.0751	likely_benign	0.0756	benign	-0.503	Destabilizing	0.001	N	0.101	neutral	N	0.420645027	None	None	I
L/K	0.2055	likely_benign	0.1966	benign	-0.757	Destabilizing	0.22	N	0.321	neutral	None	None	None	None	I
L/M	0.1294	likely_benign	0.1268	benign	-0.457	Destabilizing	0.497	N	0.276	neutral	None	None	None	None	I
L/N	0.3315	likely_benign	0.3108	benign	-0.533	Destabilizing	0.22	N	0.347	neutral	None	None	None	None	I
L/P	0.3538	ambiguous	0.3708	ambiguous	-0.657	Destabilizing	0.001	N	0.199	neutral	D	0.575014338	None	None	I
L/Q	0.1046	likely_benign	0.1054	benign	-0.738	Destabilizing	0.667	D	0.335	neutral	None	None	None	None	I
L/R	0.1308	likely_benign	0.1278	benign	-0.134	Destabilizing	0.602	D	0.354	neutral	N	0.458663396	None	None	I
L/S	0.1703	likely_benign	0.1618	benign	-1.013	Destabilizing	0.011	N	0.169	neutral	None	None	None	None	I
L/T	0.1719	likely_benign	0.1614	benign	-0.95	Destabilizing	0.004	N	0.147	neutral	None	None	None	None	I
L/V	0.0857	likely_benign	0.0865	benign	-0.657	Destabilizing	None	N	0.143	neutral	N	0.427769006	None	None	I
L/W	0.1562	likely_benign	0.1531	benign	-0.839	Destabilizing	0.883	D	0.255	neutral	None	None	None	None	I
L/Y	0.2559	likely_benign	0.2508	benign	-0.618	Destabilizing	0.124	N	0.355	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.