TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28438	85537;85538;85539	chr2:178560820;178560819;178560818	chr2:179425547;179425546;179425545
N2AB	26797	80614;80615;80616	chr2:178560820;178560819;178560818	chr2:179425547;179425546;179425545
N2A	25870	77833;77834;77835	chr2:178560820;178560819;178560818	chr2:179425547;179425546;179425545
N2B	19373	58342;58343;58344	chr2:178560820;178560819;178560818	chr2:179425547;179425546;179425545
Novex-1	19498	58717;58718;58719	chr2:178560820;178560819;178560818	chr2:179425547;179425546;179425545
Novex-2	19565	58918;58919;58920	chr2:178560820;178560819;178560818	chr2:179425547;179425546;179425545
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Ig-143
• Domain position: 81
• Structural Position: 165
• Q(SASA): 0.4454
• 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/S	None	None	0.999	N	0.607	0.23	0.317084106153	gnomAD-4.0.0	2.40064E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.625E-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	0.1122	likely_benign	0.1109	benign	-0.344	Destabilizing	0.999	D	0.583	neutral	N	0.494491421	None	None	I
T/C	0.4033	ambiguous	0.4302	ambiguous	-0.208	Destabilizing	1.0	D	0.683	prob.neutral	None	None	None	None	I
T/D	0.4473	ambiguous	0.4371	ambiguous	0.152	Stabilizing	1.0	D	0.742	deleterious	None	None	None	None	I
T/E	0.2832	likely_benign	0.2849	benign	0.063	Stabilizing	1.0	D	0.743	deleterious	None	None	None	None	I
T/F	0.2146	likely_benign	0.2189	benign	-0.911	Destabilizing	1.0	D	0.755	deleterious	None	None	None	None	I
T/G	0.3129	likely_benign	0.3064	benign	-0.448	Destabilizing	1.0	D	0.701	prob.neutral	None	None	None	None	I
T/H	0.2773	likely_benign	0.2845	benign	-0.798	Destabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	I
T/I	0.1515	likely_benign	0.1587	benign	-0.194	Destabilizing	1.0	D	0.729	prob.delet.	N	0.486808873	None	None	I
T/K	0.2424	likely_benign	0.2462	benign	-0.31	Destabilizing	1.0	D	0.745	deleterious	None	None	None	None	I
T/L	0.1202	likely_benign	0.1222	benign	-0.194	Destabilizing	0.999	D	0.681	prob.neutral	None	None	None	None	I
T/M	0.0939	likely_benign	0.0979	benign	0.038	Stabilizing	1.0	D	0.683	prob.neutral	None	None	None	None	I
T/N	0.1283	likely_benign	0.1251	benign	-0.056	Destabilizing	1.0	D	0.763	deleterious	N	0.519994246	None	None	I
T/P	0.4402	ambiguous	0.414	ambiguous	-0.217	Destabilizing	1.0	D	0.721	prob.delet.	N	0.511407588	None	None	I
T/Q	0.2212	likely_benign	0.2249	benign	-0.314	Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	I
T/R	0.2101	likely_benign	0.2158	benign	-0.055	Destabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	I
T/S	0.1067	likely_benign	0.1034	benign	-0.257	Destabilizing	0.999	D	0.607	neutral	N	0.430084318	None	None	I
T/V	0.1313	likely_benign	0.1347	benign	-0.217	Destabilizing	0.999	D	0.669	neutral	None	None	None	None	I
T/W	0.5777	likely_pathogenic	0.5825	pathogenic	-0.921	Destabilizing	1.0	D	0.716	prob.delet.	None	None	None	None	I
T/Y	0.2789	likely_benign	0.2809	benign	-0.631	Destabilizing	1.0	D	0.743	deleterious	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.