TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14709	44350;44351;44352	chr2:178630833;178630832;178630831	chr2:179495560;179495559;179495558
N2AB	13068	39427;39428;39429	chr2:178630833;178630832;178630831	chr2:179495560;179495559;179495558
N2A	12141	36646;36647;36648	chr2:178630833;178630832;178630831	chr2:179495560;179495559;179495558
N2B	5644	17155;17156;17157	chr2:178630833;178630832;178630831	chr2:179495560;179495559;179495558
Novex-1	5769	17530;17531;17532	chr2:178630833;178630832;178630831	chr2:179495560;179495559;179495558
Novex-2	5836	17731;17732;17733	chr2:178630833;178630832;178630831	chr2:179495560;179495559;179495558
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTC
• RefSeq wild type template codon: GAG
• Domain: Ig-98
• Domain position: 35
• Structural Position: 50
• Q(SASA): 0.2033
• 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
L/I	None	None	0.997	D	0.573	0.301	0.444102476654	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	6.33473E-05	0	None	0	0	None	0	0	0	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
L/A	0.9142	likely_pathogenic	0.9468	pathogenic	-2.028	Highly Destabilizing	0.998	D	0.726	deleterious	None	None	None	None	N
L/C	0.8905	likely_pathogenic	0.9278	pathogenic	-1.479	Destabilizing	1.0	D	0.759	deleterious	None	None	None	None	N
L/D	0.9879	likely_pathogenic	0.9919	pathogenic	-1.202	Destabilizing	1.0	D	0.86	deleterious	None	None	None	None	N
L/E	0.943	likely_pathogenic	0.9597	pathogenic	-1.138	Destabilizing	0.999	D	0.861	deleterious	None	None	None	None	N
L/F	0.3914	ambiguous	0.4899	ambiguous	-1.294	Destabilizing	0.999	D	0.752	deleterious	D	0.542354601	None	None	N
L/G	0.9656	likely_pathogenic	0.9766	pathogenic	-2.429	Highly Destabilizing	0.999	D	0.838	deleterious	None	None	None	None	N
L/H	0.7861	likely_pathogenic	0.8668	pathogenic	-1.51	Destabilizing	1.0	D	0.833	deleterious	D	0.543123139	None	None	N
L/I	0.1967	likely_benign	0.2505	benign	-0.964	Destabilizing	0.997	D	0.573	neutral	D	0.581181237	None	None	N
L/K	0.8283	likely_pathogenic	0.8804	pathogenic	-1.411	Destabilizing	0.999	D	0.85	deleterious	None	None	None	None	N
L/M	0.2622	likely_benign	0.34	ambiguous	-0.862	Destabilizing	0.999	D	0.739	deleterious	None	None	None	None	N
L/N	0.9355	likely_pathogenic	0.9615	pathogenic	-1.31	Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
L/P	0.9885	likely_pathogenic	0.9915	pathogenic	-1.289	Destabilizing	1.0	D	0.867	deleterious	D	0.583982092	None	None	N
L/Q	0.7324	likely_pathogenic	0.8336	pathogenic	-1.409	Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
L/R	0.7196	likely_pathogenic	0.7974	pathogenic	-0.858	Destabilizing	0.999	D	0.853	deleterious	N	0.414454862	None	None	N
L/S	0.9518	likely_pathogenic	0.9745	pathogenic	-2.087	Highly Destabilizing	0.999	D	0.841	deleterious	None	None	None	None	N
L/T	0.9189	likely_pathogenic	0.9526	pathogenic	-1.887	Destabilizing	0.999	D	0.828	deleterious	None	None	None	None	N
L/V	0.2962	likely_benign	0.3887	ambiguous	-1.289	Destabilizing	0.997	D	0.569	neutral	D	0.542354601	None	None	N
L/W	0.5353	ambiguous	0.6658	pathogenic	-1.346	Destabilizing	1.0	D	0.756	deleterious	None	None	None	None	N
L/Y	0.6735	likely_pathogenic	0.7872	pathogenic	-1.148	Destabilizing	0.999	D	0.807	deleterious	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.