TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6628	20107;20108;20109	chr2:178727696;178727695;178727694	chr2:179592423;179592422;179592421
N2AB	6311	19156;19157;19158	chr2:178727696;178727695;178727694	chr2:179592423;179592422;179592421
N2A	5384	16375;16376;16377	chr2:178727696;178727695;178727694	chr2:179592423;179592422;179592421
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: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Ig-50
• Domain position: 55
• Structural Position: 135
• Q(SASA): 0.2326
• Predicted PPI site: N

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/P	None	None	0.937	D	0.607	0.507	0.476754456241	gnomAD-4.0.0	6.00161E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	6.56251E-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	0.08	likely_benign	0.0785	benign	-1.122	Destabilizing	0.123	N	0.448	neutral	N	0.500947126	None	None	N
T/C	0.4612	ambiguous	0.4307	ambiguous	-0.576	Destabilizing	0.999	D	0.603	neutral	None	None	None	None	N
T/D	0.3555	ambiguous	0.3232	benign	0.069	Stabilizing	0.735	D	0.562	neutral	None	None	None	None	N
T/E	0.2515	likely_benign	0.2346	benign	0.158	Stabilizing	0.902	D	0.559	neutral	None	None	None	None	N
T/F	0.2358	likely_benign	0.2137	benign	-0.981	Destabilizing	0.992	D	0.633	neutral	None	None	None	None	N
T/G	0.2742	likely_benign	0.2656	benign	-1.449	Destabilizing	0.959	D	0.579	neutral	None	None	None	None	N
T/H	0.2475	likely_benign	0.2333	benign	-1.498	Destabilizing	0.999	D	0.635	neutral	None	None	None	None	N
T/I	0.1483	likely_benign	0.1398	benign	-0.307	Destabilizing	0.03	N	0.372	neutral	N	0.450056945	None	None	N
T/K	0.1933	likely_benign	0.1824	benign	-0.333	Destabilizing	0.928	D	0.561	neutral	None	None	None	None	N
T/L	0.1108	likely_benign	0.1059	benign	-0.307	Destabilizing	0.728	D	0.517	neutral	None	None	None	None	N
T/M	0.1052	likely_benign	0.1047	benign	-0.171	Destabilizing	0.978	D	0.617	neutral	None	None	None	None	N
T/N	0.1274	likely_benign	0.1216	benign	-0.498	Destabilizing	0.677	D	0.517	neutral	N	0.467103911	None	None	N
T/P	0.2892	likely_benign	0.2686	benign	-0.547	Destabilizing	0.937	D	0.607	neutral	D	0.531616749	None	None	N
T/Q	0.2	likely_benign	0.2038	benign	-0.516	Destabilizing	0.977	D	0.623	neutral	None	None	None	None	N
T/R	0.1393	likely_benign	0.1286	benign	-0.312	Destabilizing	0.996	D	0.612	neutral	None	None	None	None	N
T/S	0.1065	likely_benign	0.1033	benign	-0.948	Destabilizing	0.011	N	0.205	neutral	N	0.402745788	None	None	N
T/V	0.1182	likely_benign	0.1186	benign	-0.547	Destabilizing	0.656	D	0.496	neutral	None	None	None	None	N
T/W	0.5911	likely_pathogenic	0.5682	pathogenic	-0.871	Destabilizing	1.0	D	0.671	neutral	None	None	None	None	N
T/Y	0.2608	likely_benign	0.2449	benign	-0.608	Destabilizing	0.999	D	0.65	neutral	None	None	None	None	N

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.