TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1546	4861;4862;4863	chr2:178777429;178777428;178777427	chr2:179642156;179642155;179642154
N2AB	1546	4861;4862;4863	chr2:178777429;178777428;178777427	chr2:179642156;179642155;179642154
N2A	1546	4861;4862;4863	chr2:178777429;178777428;178777427	chr2:179642156;179642155;179642154
N2B	1500	4723;4724;4725	chr2:178777429;178777428;178777427	chr2:179642156;179642155;179642154
Novex-1	1500	4723;4724;4725	chr2:178777429;178777428;178777427	chr2:179642156;179642155;179642154
Novex-2	1500	4723;4724;4725	chr2:178777429;178777428;178777427	chr2:179642156;179642155;179642154
Novex-3	1546	4861;4862;4863	chr2:178777429;178777428;178777427	chr2:179642156;179642155;179642154

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Ig-6
• Domain position: 90
• Structural Position: 175
• Q(SASA): 0.3303
• 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/A	None	None	0.64	N	0.531	0.31	0.394990421082	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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	0.0958	likely_benign	0.0965	benign	-0.86	Destabilizing	0.64	D	0.531	neutral	N	0.513531673	None	None	N
T/C	0.4975	ambiguous	0.5261	ambiguous	-0.575	Destabilizing	0.999	D	0.587	neutral	None	None	None	None	N
T/D	0.3104	likely_benign	0.3105	benign	-0.097	Destabilizing	0.976	D	0.537	neutral	None	None	None	None	N
T/E	0.2525	likely_benign	0.2584	benign	-0.093	Destabilizing	0.976	D	0.545	neutral	None	None	None	None	N
T/F	0.2572	likely_benign	0.2666	benign	-0.891	Destabilizing	0.988	D	0.673	neutral	None	None	None	None	N
T/G	0.3212	likely_benign	0.3421	ambiguous	-1.119	Destabilizing	0.851	D	0.645	neutral	None	None	None	None	N
T/H	0.1692	likely_benign	0.1745	benign	-1.34	Destabilizing	0.999	D	0.681	prob.neutral	None	None	None	None	N
T/I	0.2038	likely_benign	0.2091	benign	-0.262	Destabilizing	0.211	N	0.328	neutral	N	0.515612042	None	None	N
T/K	0.1862	likely_benign	0.1838	benign	-0.704	Destabilizing	0.976	D	0.542	neutral	None	None	None	None	N
T/L	0.1186	likely_benign	0.122	benign	-0.262	Destabilizing	0.851	D	0.573	neutral	None	None	None	None	N
T/M	0.0963	likely_benign	0.1005	benign	-0.013	Destabilizing	0.997	D	0.577	neutral	None	None	None	None	N
T/N	0.0956	likely_benign	0.0955	benign	-0.645	Destabilizing	0.968	D	0.487	neutral	N	0.49710086	None	None	N
T/P	0.5488	ambiguous	0.548	ambiguous	-0.429	Destabilizing	0.984	D	0.568	neutral	D	0.705840749	None	None	N
T/Q	0.1897	likely_benign	0.1954	benign	-0.815	Destabilizing	0.988	D	0.579	neutral	None	None	None	None	N
T/R	0.1593	likely_benign	0.1553	benign	-0.471	Destabilizing	0.976	D	0.575	neutral	None	None	None	None	N
T/S	0.1022	likely_benign	0.1079	benign	-0.974	Destabilizing	0.103	N	0.199	neutral	N	0.512264129	None	None	N
T/V	0.1769	likely_benign	0.1832	benign	-0.429	Destabilizing	0.851	D	0.534	neutral	None	None	None	None	N
T/W	0.5879	likely_pathogenic	0.6138	pathogenic	-0.79	Destabilizing	0.999	D	0.731	prob.delet.	None	None	None	None	N
T/Y	0.2869	likely_benign	0.2981	benign	-0.569	Destabilizing	0.996	D	0.684	prob.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.