TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19993	60202;60203;60204	chr2:178591842;178591841;178591840	chr2:179456569;179456568;179456567
N2AB	18352	55279;55280;55281	chr2:178591842;178591841;178591840	chr2:179456569;179456568;179456567
N2A	17425	52498;52499;52500	chr2:178591842;178591841;178591840	chr2:179456569;179456568;179456567
N2B	10928	33007;33008;33009	chr2:178591842;178591841;178591840	chr2:179456569;179456568;179456567
Novex-1	11053	33382;33383;33384	chr2:178591842;178591841;178591840	chr2:179456569;179456568;179456567
Novex-2	11120	33583;33584;33585	chr2:178591842;178591841;178591840	chr2:179456569;179456568;179456567
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: Fn3-33
• Domain position: 17
• Structural Position: 19
• Q(SASA): 0.2105
• 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/Q	None	None	0.957	N	0.326	0.176	0.267299060538	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-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	0.2649	likely_benign	0.1915	benign	-0.584	Destabilizing	0.996	D	0.633	neutral	N	0.442290319	None	None	N
E/C	0.9175	likely_pathogenic	0.8937	pathogenic	-0.431	Destabilizing	1.0	D	0.844	deleterious	None	None	None	None	N
E/D	0.5154	ambiguous	0.4025	ambiguous	-1.333	Destabilizing	0.996	D	0.509	neutral	N	0.508533954	None	None	N
E/F	0.9338	likely_pathogenic	0.9026	pathogenic	-0.711	Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	N
E/G	0.4663	ambiguous	0.3438	ambiguous	-0.916	Destabilizing	0.999	D	0.777	deleterious	N	0.482136786	None	None	N
E/H	0.7141	likely_pathogenic	0.6155	pathogenic	-1.12	Destabilizing	1.0	D	0.754	deleterious	None	None	None	None	N
E/I	0.7386	likely_pathogenic	0.6325	pathogenic	0.306	Stabilizing	1.0	D	0.857	deleterious	None	None	None	None	N
E/K	0.3965	ambiguous	0.2661	benign	-0.707	Destabilizing	0.992	D	0.511	neutral	N	0.512515622	None	None	N
E/L	0.8121	likely_pathogenic	0.7198	pathogenic	0.306	Stabilizing	1.0	D	0.84	deleterious	None	None	None	None	N
E/M	0.6881	likely_pathogenic	0.5897	pathogenic	0.758	Stabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
E/N	0.6036	likely_pathogenic	0.4673	ambiguous	-0.945	Destabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	N
E/P	0.9976	likely_pathogenic	0.9974	pathogenic	0.032	Stabilizing	1.0	D	0.838	deleterious	None	None	None	None	N
E/Q	0.2292	likely_benign	0.1762	benign	-0.823	Destabilizing	0.957	D	0.326	neutral	N	0.4798272	None	None	N
E/R	0.5382	ambiguous	0.4292	ambiguous	-0.706	Destabilizing	0.999	D	0.725	prob.delet.	None	None	None	None	N
E/S	0.3475	ambiguous	0.2556	benign	-1.315	Destabilizing	0.997	D	0.601	neutral	None	None	None	None	N
E/T	0.3696	ambiguous	0.2687	benign	-1.036	Destabilizing	1.0	D	0.794	deleterious	None	None	None	None	N
E/V	0.4819	ambiguous	0.3866	ambiguous	0.032	Stabilizing	0.999	D	0.831	deleterious	N	0.484099656	None	None	N
E/W	0.9777	likely_pathogenic	0.9666	pathogenic	-0.799	Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
E/Y	0.8842	likely_pathogenic	0.8388	pathogenic	-0.529	Destabilizing	1.0	D	0.853	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.