TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18697	56314;56315;56316	chr2:178599812;178599811;178599810	chr2:179464539;179464538;179464537
N2AB	17056	51391;51392;51393	chr2:178599812;178599811;178599810	chr2:179464539;179464538;179464537
N2A	16129	48610;48611;48612	chr2:178599812;178599811;178599810	chr2:179464539;179464538;179464537
N2B	9632	29119;29120;29121	chr2:178599812;178599811;178599810	chr2:179464539;179464538;179464537
Novex-1	9757	29494;29495;29496	chr2:178599812;178599811;178599810	chr2:179464539;179464538;179464537
Novex-2	9824	29695;29696;29697	chr2:178599812;178599811;178599810	chr2:179464539;179464538;179464537
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-116
• Domain position: 10
• Structural Position: 18
• Q(SASA): 0.7314
• 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/D	rs767433299	-0.15	0.996	N	0.541	0.219	0.288727942641	gnomAD-2.1.1	4.17E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	9.11E-06	0
E/D	rs767433299	-0.15	0.996	N	0.541	0.219	0.288727942641	gnomAD-4.0.0	1.61808E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.89149E-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	0.1854	likely_benign	0.1755	benign	-0.436	Destabilizing	0.619	D	0.447	neutral	N	0.469277424	None	None	N
E/C	0.8881	likely_pathogenic	0.8972	pathogenic	-0.098	Destabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	N
E/D	0.283	likely_benign	0.3248	benign	-0.38	Destabilizing	0.996	D	0.541	neutral	N	0.513606992	None	None	N
E/F	0.8561	likely_pathogenic	0.8663	pathogenic	-0.289	Destabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	N
E/G	0.313	likely_benign	0.3239	benign	-0.631	Destabilizing	0.984	D	0.65	neutral	D	0.52769101	None	None	N
E/H	0.6508	likely_pathogenic	0.6803	pathogenic	-0.028	Destabilizing	1.0	D	0.653	neutral	None	None	None	None	N
E/I	0.4355	ambiguous	0.4309	ambiguous	0.045	Stabilizing	0.999	D	0.714	prob.delet.	None	None	None	None	N
E/K	0.175	likely_benign	0.2064	benign	0.308	Stabilizing	0.992	D	0.642	neutral	N	0.474779245	None	None	N
E/L	0.442	ambiguous	0.4408	ambiguous	0.045	Stabilizing	0.998	D	0.661	neutral	None	None	None	None	N
E/M	0.525	ambiguous	0.511	ambiguous	0.135	Stabilizing	1.0	D	0.69	prob.neutral	None	None	None	None	N
E/N	0.4582	ambiguous	0.4979	ambiguous	-0.067	Destabilizing	1.0	D	0.685	prob.neutral	None	None	None	None	N
E/P	0.431	ambiguous	0.4839	ambiguous	-0.095	Destabilizing	0.999	D	0.67	neutral	None	None	None	None	N
E/Q	0.1701	likely_benign	0.1783	benign	-0.031	Destabilizing	1.0	D	0.603	neutral	N	0.490306058	None	None	N
E/R	0.296	likely_benign	0.339	benign	0.523	Stabilizing	0.999	D	0.683	prob.neutral	None	None	None	None	N
E/S	0.3438	ambiguous	0.3514	ambiguous	-0.214	Destabilizing	0.988	D	0.642	neutral	None	None	None	None	N
E/T	0.3005	likely_benign	0.2936	benign	-0.052	Destabilizing	0.998	D	0.63	neutral	None	None	None	None	N
E/V	0.2556	likely_benign	0.244	benign	-0.095	Destabilizing	0.998	D	0.612	neutral	N	0.475070033	None	None	N
E/W	0.9439	likely_pathogenic	0.9537	pathogenic	-0.121	Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	N
E/Y	0.7785	likely_pathogenic	0.8118	pathogenic	-0.044	Destabilizing	1.0	D	0.7	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.