TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30263	91012;91013;91014	chr2:178552113;178552112;178552111	chr2:179416840;179416839;179416838
N2AB	28622	86089;86090;86091	chr2:178552113;178552112;178552111	chr2:179416840;179416839;179416838
N2A	27695	83308;83309;83310	chr2:178552113;178552112;178552111	chr2:179416840;179416839;179416838
N2B	21198	63817;63818;63819	chr2:178552113;178552112;178552111	chr2:179416840;179416839;179416838
Novex-1	21323	64192;64193;64194	chr2:178552113;178552112;178552111	chr2:179416840;179416839;179416838
Novex-2	21390	64393;64394;64395	chr2:178552113;178552112;178552111	chr2:179416840;179416839;179416838
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Fn3-108
• Domain position: 40
• Structural Position: 41
• Q(SASA): 0.1199
• 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
E/K	rs745701838	-2.175	1.0	N	0.693	0.457	0.423002944196	gnomAD-2.1.1	1.21E-05	None	None	None	None	N	None	0	0	None	0	5.57E-05	None	0	None	0	1.78E-05	0
E/K	rs745701838	-2.175	1.0	N	0.693	0.457	0.423002944196	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	4.83E-05	0	0	0	0	None	0	0	0	0	0
E/K	rs745701838	-2.175	1.0	N	0.693	0.457	0.423002944196	gnomAD-4.0.0	6.81697E-06	None	None	None	None	N	None	2.6703E-05	0	None	0	8.91345E-05	None	0	0	4.23811E-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
E/A	0.9494	likely_pathogenic	0.9316	pathogenic	-2.379	Highly Destabilizing	0.999	D	0.689	prob.neutral	D	0.538812282	None	None	N
E/C	0.9902	likely_pathogenic	0.9899	pathogenic	-1.388	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
E/D	0.8684	likely_pathogenic	0.7578	pathogenic	-1.919	Destabilizing	0.999	D	0.659	neutral	N	0.480473819	None	None	N
E/F	0.9944	likely_pathogenic	0.9931	pathogenic	-2.132	Highly Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
E/G	0.9534	likely_pathogenic	0.9361	pathogenic	-2.732	Highly Destabilizing	1.0	D	0.742	deleterious	D	0.533838759	None	None	N
E/H	0.9817	likely_pathogenic	0.9774	pathogenic	-1.878	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
E/I	0.986	likely_pathogenic	0.9831	pathogenic	-1.349	Destabilizing	1.0	D	0.81	deleterious	None	None	None	None	N
E/K	0.9577	likely_pathogenic	0.9483	pathogenic	-2.17	Highly Destabilizing	1.0	D	0.693	prob.neutral	N	0.519440579	None	None	N
E/L	0.9782	likely_pathogenic	0.9731	pathogenic	-1.349	Destabilizing	1.0	D	0.764	deleterious	None	None	None	None	N
E/M	0.9784	likely_pathogenic	0.9724	pathogenic	-0.528	Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	N
E/N	0.9888	likely_pathogenic	0.9794	pathogenic	-2.237	Highly Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
E/P	0.9998	likely_pathogenic	0.9997	pathogenic	-1.683	Destabilizing	1.0	D	0.766	deleterious	None	None	None	None	N
E/Q	0.699	likely_pathogenic	0.6577	pathogenic	-2.0	Highly Destabilizing	1.0	D	0.763	deleterious	N	0.50280006	None	None	N
E/R	0.964	likely_pathogenic	0.96	pathogenic	-1.858	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
E/S	0.949	likely_pathogenic	0.9237	pathogenic	-2.96	Highly Destabilizing	0.999	D	0.751	deleterious	None	None	None	None	N
E/T	0.9802	likely_pathogenic	0.9716	pathogenic	-2.618	Highly Destabilizing	1.0	D	0.769	deleterious	None	None	None	None	N
E/V	0.9666	likely_pathogenic	0.9575	pathogenic	-1.683	Destabilizing	1.0	D	0.727	prob.delet.	N	0.516695555	None	None	N
E/W	0.9962	likely_pathogenic	0.9954	pathogenic	-2.123	Highly Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
E/Y	0.9917	likely_pathogenic	0.9895	pathogenic	-1.952	Destabilizing	1.0	D	0.787	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.