TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	34376	103351;103352;103353	chr2:178533489;178533488;178533487	chr2:179398216;179398215;179398214
N2AB	32735	98428;98429;98430	chr2:178533489;178533488;178533487	chr2:179398216;179398215;179398214
N2A	31808	95647;95648;95649	chr2:178533489;178533488;178533487	chr2:179398216;179398215;179398214
N2B	25311	76156;76157;76158	chr2:178533489;178533488;178533487	chr2:179398216;179398215;179398214
Novex-1	25436	76531;76532;76533	chr2:178533489;178533488;178533487	chr2:179398216;179398215;179398214
Novex-2	25503	76732;76733;76734	chr2:178533489;178533488;178533487	chr2:179398216;179398215;179398214
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-162
• Domain position: 14
• Structural Position: 23
• Q(SASA): 0.516
• 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/V	None	None	1.0	D	0.69	0.613	0.704318944212	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
E/A	0.6246	likely_pathogenic	0.6241	pathogenic	-0.745	Destabilizing	0.999	D	0.582	neutral	D	0.531752822	None	None	N
E/C	0.9941	likely_pathogenic	0.9936	pathogenic	-0.255	Destabilizing	1.0	D	0.745	deleterious	None	None	None	None	N
E/D	0.8976	likely_pathogenic	0.8955	pathogenic	-0.654	Destabilizing	0.999	D	0.433	neutral	N	0.493004299	None	None	N
E/F	0.9972	likely_pathogenic	0.9966	pathogenic	-0.445	Destabilizing	1.0	D	0.713	prob.delet.	None	None	None	None	N
E/G	0.8715	likely_pathogenic	0.8582	pathogenic	-1.005	Destabilizing	1.0	D	0.625	neutral	D	0.533264961	None	None	N
E/H	0.988	likely_pathogenic	0.986	pathogenic	-0.423	Destabilizing	1.0	D	0.642	neutral	None	None	None	None	N
E/I	0.929	likely_pathogenic	0.9292	pathogenic	-0.068	Destabilizing	1.0	D	0.736	prob.delet.	None	None	None	None	N
E/K	0.8543	likely_pathogenic	0.8573	pathogenic	-0.059	Destabilizing	0.999	D	0.598	neutral	N	0.49899178	None	None	N
E/L	0.9681	likely_pathogenic	0.9705	pathogenic	-0.068	Destabilizing	1.0	D	0.716	prob.delet.	None	None	None	None	N
E/M	0.9605	likely_pathogenic	0.9599	pathogenic	0.214	Stabilizing	1.0	D	0.659	neutral	None	None	None	None	N
E/N	0.9717	likely_pathogenic	0.9686	pathogenic	-0.482	Destabilizing	1.0	D	0.684	prob.neutral	None	None	None	None	N
E/P	0.947	likely_pathogenic	0.9421	pathogenic	-0.273	Destabilizing	1.0	D	0.622	neutral	None	None	None	None	N
E/Q	0.7303	likely_pathogenic	0.7009	pathogenic	-0.423	Destabilizing	1.0	D	0.614	neutral	N	0.490370953	None	None	N
E/R	0.9179	likely_pathogenic	0.9173	pathogenic	0.187	Stabilizing	1.0	D	0.675	prob.neutral	None	None	None	None	N
E/S	0.8947	likely_pathogenic	0.8832	pathogenic	-0.678	Destabilizing	0.999	D	0.648	neutral	None	None	None	None	N
E/T	0.9018	likely_pathogenic	0.9075	pathogenic	-0.463	Destabilizing	1.0	D	0.643	neutral	None	None	None	None	N
E/V	0.7922	likely_pathogenic	0.8076	pathogenic	-0.273	Destabilizing	1.0	D	0.69	prob.neutral	D	0.523650627	None	None	N
E/W	0.999	likely_pathogenic	0.9988	pathogenic	-0.203	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	N
E/Y	0.9934	likely_pathogenic	0.9922	pathogenic	-0.19	Destabilizing	1.0	D	0.687	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.