TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35724	107395;107396;107397	chr2:178528581;178528580;178528579	chr2:179393308;179393307;179393306
N2AB	34083	102472;102473;102474	chr2:178528581;178528580;178528579	chr2:179393308;179393307;179393306
N2A	33156	99691;99692;99693	chr2:178528581;178528580;178528579	chr2:179393308;179393307;179393306
N2B	26659	80200;80201;80202	chr2:178528581;178528580;178528579	chr2:179393308;179393307;179393306
Novex-1	26784	80575;80576;80577	chr2:178528581;178528580;178528579	chr2:179393308;179393307;179393306
Novex-2	26851	80776;80777;80778	chr2:178528581;178528580;178528579	chr2:179393308;179393307;179393306
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-168
• Domain position: 23
• Structural Position: 34
• Q(SASA): 0.2729
• 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	None	None	0.998	N	0.417	0.205	0.358540694251	gnomAD-4.0.0	6.84635E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.16168E-05	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	0.3523	ambiguous	0.3078	benign	-1.22	Destabilizing	0.994	D	0.551	neutral	N	0.469874857	None	None	N
E/C	0.9717	likely_pathogenic	0.9693	pathogenic	-0.58	Destabilizing	1.0	D	0.752	deleterious	None	None	None	None	N
E/D	0.3685	ambiguous	0.3233	benign	-1.233	Destabilizing	0.998	D	0.417	neutral	N	0.485671029	None	None	N
E/F	0.9381	likely_pathogenic	0.9173	pathogenic	-0.844	Destabilizing	0.998	D	0.77	deleterious	None	None	None	None	N
E/G	0.4958	ambiguous	0.4381	ambiguous	-1.582	Destabilizing	0.999	D	0.705	prob.neutral	D	0.52882716	None	None	N
E/H	0.7452	likely_pathogenic	0.6975	pathogenic	-1.04	Destabilizing	1.0	D	0.723	prob.delet.	None	None	None	None	N
E/I	0.6758	likely_pathogenic	0.6119	pathogenic	-0.223	Destabilizing	0.995	D	0.724	prob.delet.	None	None	None	None	N
E/K	0.2871	likely_benign	0.2443	benign	-0.635	Destabilizing	0.998	D	0.471	neutral	N	0.453134536	None	None	N
E/L	0.7636	likely_pathogenic	0.6971	pathogenic	-0.223	Destabilizing	0.269	N	0.603	neutral	None	None	None	None	N
E/M	0.7049	likely_pathogenic	0.6619	pathogenic	0.372	Stabilizing	0.999	D	0.765	deleterious	None	None	None	None	N
E/N	0.5259	ambiguous	0.4539	ambiguous	-1.084	Destabilizing	1.0	D	0.711	prob.delet.	None	None	None	None	N
E/P	0.9788	likely_pathogenic	0.9702	pathogenic	-0.536	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
E/Q	0.2155	likely_benign	0.1907	benign	-0.982	Destabilizing	0.999	D	0.635	neutral	N	0.458945788	None	None	N
E/R	0.479	ambiguous	0.4231	ambiguous	-0.447	Destabilizing	1.0	D	0.711	prob.delet.	None	None	None	None	N
E/S	0.401	ambiguous	0.3485	ambiguous	-1.498	Destabilizing	0.999	D	0.544	neutral	None	None	None	None	N
E/T	0.4223	ambiguous	0.3558	ambiguous	-1.177	Destabilizing	0.999	D	0.727	prob.delet.	None	None	None	None	N
E/V	0.4642	ambiguous	0.4115	ambiguous	-0.536	Destabilizing	0.978	D	0.646	neutral	N	0.492733074	None	None	N
E/W	0.9838	likely_pathogenic	0.9786	pathogenic	-0.581	Destabilizing	1.0	D	0.749	deleterious	None	None	None	None	N
E/Y	0.8945	likely_pathogenic	0.867	pathogenic	-0.55	Destabilizing	1.0	D	0.771	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.