TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	34977	105154;105155;105156	chr2:178531686;178531685;178531684	chr2:179396413;179396412;179396411
N2AB	33336	100231;100232;100233	chr2:178531686;178531685;178531684	chr2:179396413;179396412;179396411
N2A	32409	97450;97451;97452	chr2:178531686;178531685;178531684	chr2:179396413;179396412;179396411
N2B	25912	77959;77960;77961	chr2:178531686;178531685;178531684	chr2:179396413;179396412;179396411
Novex-1	26037	78334;78335;78336	chr2:178531686;178531685;178531684	chr2:179396413;179396412;179396411
Novex-2	26104	78535;78536;78537	chr2:178531686;178531685;178531684	chr2:179396413;179396412;179396411
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: H
• RefSeq wild type transcript codon: CAC
• RefSeq wild type template codon: GTG
• Domain: Ig-163
• Domain position: 36
• Structural Position: 50
• Q(SASA): 0.134
• 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
H/Q	None	None	1.0	N	0.673	0.379	0.162503812791	gnomAD-4.0.0	1.59089E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85757E-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
H/A	0.9301	likely_pathogenic	0.9756	pathogenic	-1.189	Destabilizing	0.999	D	0.642	neutral	None	None	None	None	N
H/C	0.4578	ambiguous	0.6328	pathogenic	-0.562	Destabilizing	1.0	D	0.818	deleterious	None	None	None	None	N
H/D	0.9507	likely_pathogenic	0.9824	pathogenic	-0.503	Destabilizing	1.0	D	0.671	neutral	N	0.49040614	None	None	N
H/E	0.9315	likely_pathogenic	0.9771	pathogenic	-0.387	Destabilizing	0.999	D	0.535	neutral	None	None	None	None	N
H/F	0.7901	likely_pathogenic	0.8883	pathogenic	-0.106	Destabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	N
H/G	0.9542	likely_pathogenic	0.9843	pathogenic	-1.556	Destabilizing	0.999	D	0.663	neutral	None	None	None	None	N
H/I	0.9176	likely_pathogenic	0.9722	pathogenic	-0.166	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
H/K	0.6507	likely_pathogenic	0.7996	pathogenic	-0.78	Destabilizing	1.0	D	0.667	neutral	None	None	None	None	N
H/L	0.5673	likely_pathogenic	0.753	pathogenic	-0.166	Destabilizing	1.0	D	0.759	deleterious	N	0.46499405	None	None	N
H/M	0.9406	likely_pathogenic	0.9764	pathogenic	-0.341	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
H/N	0.6626	likely_pathogenic	0.8152	pathogenic	-0.927	Destabilizing	0.999	D	0.549	neutral	N	0.504597067	None	None	N
H/P	0.9792	likely_pathogenic	0.9937	pathogenic	-0.489	Destabilizing	1.0	D	0.747	deleterious	N	0.467528945	None	None	N
H/Q	0.615	likely_pathogenic	0.8074	pathogenic	-0.701	Destabilizing	1.0	D	0.673	neutral	N	0.489899161	None	None	N
H/R	0.2401	likely_benign	0.4137	ambiguous	-0.949	Destabilizing	1.0	D	0.662	neutral	N	0.475810168	None	None	N
H/S	0.8837	likely_pathogenic	0.9534	pathogenic	-1.189	Destabilizing	1.0	D	0.657	neutral	None	None	None	None	N
H/T	0.9555	likely_pathogenic	0.9874	pathogenic	-0.963	Destabilizing	1.0	D	0.734	prob.delet.	None	None	None	None	N
H/V	0.8812	likely_pathogenic	0.9546	pathogenic	-0.489	Destabilizing	1.0	D	0.77	deleterious	None	None	None	None	N
H/W	0.7481	likely_pathogenic	0.8649	pathogenic	0.291	Stabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
H/Y	0.3121	likely_benign	0.4816	ambiguous	0.417	Stabilizing	0.999	D	0.613	neutral	N	0.455412171	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.