TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35642	107149;107150;107151	chr2:178528827;178528826;178528825	chr2:179393554;179393553;179393552
N2AB	34001	102226;102227;102228	chr2:178528827;178528826;178528825	chr2:179393554;179393553;179393552
N2A	33074	99445;99446;99447	chr2:178528827;178528826;178528825	chr2:179393554;179393553;179393552
N2B	26577	79954;79955;79956	chr2:178528827;178528826;178528825	chr2:179393554;179393553;179393552
Novex-1	26702	80329;80330;80331	chr2:178528827;178528826;178528825	chr2:179393554;179393553;179393552
Novex-2	26769	80530;80531;80532	chr2:178528827;178528826;178528825	chr2:179393554;179393553;179393552
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGC
• RefSeq wild type template codon: CCG
• Domain: Ig-167
• Domain position: 36
• Structural Position: 52
• Q(SASA): 0.493
• 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
G/D	rs1553480410	None	1.0	N	0.594	0.59	0.396645960531	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	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
G/A	0.464	ambiguous	0.4759	ambiguous	-0.353	Destabilizing	1.0	D	0.486	neutral	N	0.470532926	None	None	I
G/C	0.7188	likely_pathogenic	0.7419	pathogenic	-1.065	Destabilizing	1.0	D	0.723	prob.delet.	N	0.47122636	None	None	I
G/D	0.2755	likely_benign	0.2781	benign	-0.752	Destabilizing	1.0	D	0.594	neutral	N	0.468452626	None	None	I
G/E	0.4284	ambiguous	0.446	ambiguous	-0.912	Destabilizing	1.0	D	0.663	neutral	None	None	None	None	I
G/F	0.9589	likely_pathogenic	0.9608	pathogenic	-1.072	Destabilizing	1.0	D	0.726	prob.delet.	None	None	None	None	I
G/H	0.7048	likely_pathogenic	0.6986	pathogenic	-0.412	Destabilizing	1.0	D	0.691	prob.neutral	None	None	None	None	I
G/I	0.917	likely_pathogenic	0.9218	pathogenic	-0.583	Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	I
G/K	0.6621	likely_pathogenic	0.6723	pathogenic	-0.869	Destabilizing	1.0	D	0.661	neutral	None	None	None	None	I
G/L	0.923	likely_pathogenic	0.9223	pathogenic	-0.583	Destabilizing	1.0	D	0.695	prob.neutral	None	None	None	None	I
G/M	0.9165	likely_pathogenic	0.9133	pathogenic	-0.712	Destabilizing	1.0	D	0.718	prob.delet.	None	None	None	None	I
G/N	0.3836	ambiguous	0.3763	ambiguous	-0.601	Destabilizing	1.0	D	0.649	neutral	None	None	None	None	I
G/P	0.9959	likely_pathogenic	0.9963	pathogenic	-0.48	Destabilizing	1.0	D	0.67	neutral	None	None	None	None	I
G/Q	0.5748	likely_pathogenic	0.5706	pathogenic	-0.879	Destabilizing	1.0	D	0.691	prob.neutral	None	None	None	None	I
G/R	0.5082	ambiguous	0.5147	ambiguous	-0.388	Destabilizing	1.0	D	0.671	neutral	N	0.470359568	None	None	I
G/S	0.1833	likely_benign	0.1789	benign	-0.725	Destabilizing	1.0	D	0.655	neutral	N	0.469492776	None	None	I
G/T	0.6115	likely_pathogenic	0.613	pathogenic	-0.821	Destabilizing	1.0	D	0.663	neutral	None	None	None	None	I
G/V	0.8588	likely_pathogenic	0.8662	pathogenic	-0.48	Destabilizing	1.0	D	0.686	prob.neutral	N	0.47122636	None	None	I
G/W	0.8842	likely_pathogenic	0.8858	pathogenic	-1.174	Destabilizing	1.0	D	0.697	prob.neutral	None	None	None	None	I
G/Y	0.8728	likely_pathogenic	0.8781	pathogenic	-0.876	Destabilizing	1.0	D	0.712	prob.delet.	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.