TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17291	52096;52097;52098	chr2:178609439;178609438;178609437	chr2:179474166;179474165;179474164
N2AB	15650	47173;47174;47175	chr2:178609439;178609438;178609437	chr2:179474166;179474165;179474164
N2A	14723	44392;44393;44394	chr2:178609439;178609438;178609437	chr2:179474166;179474165;179474164
N2B	8226	24901;24902;24903	chr2:178609439;178609438;178609437	chr2:179474166;179474165;179474164
Novex-1	8351	25276;25277;25278	chr2:178609439;178609438;178609437	chr2:179474166;179474165;179474164
Novex-2	8418	25477;25478;25479	chr2:178609439;178609438;178609437	chr2:179474166;179474165;179474164
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: Ig-112
• Domain position: 41
• Structural Position: 73
• Q(SASA): 0.0681
• 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	0.984	N	0.721	0.214	0.391775403332	gnomAD-4.0.0	1.59434E-06	None	None	None	None	N	None	5.67666E-05	0	None	0	0	None	0	0	0	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	0.1706	likely_benign	0.1643	benign	-0.552	Destabilizing	0.103	N	0.536	neutral	D	0.530515097	None	None	N
E/C	0.8527	likely_pathogenic	0.8407	pathogenic	-0.219	Destabilizing	0.999	D	0.85	deleterious	None	None	None	None	N
E/D	0.1801	likely_benign	0.1748	benign	-0.623	Destabilizing	0.896	D	0.693	prob.neutral	D	0.531381889	None	None	N
E/F	0.7971	likely_pathogenic	0.7866	pathogenic	-0.297	Destabilizing	0.988	D	0.871	deleterious	None	None	None	None	N
E/G	0.1787	likely_benign	0.1654	benign	-0.809	Destabilizing	0.896	D	0.749	deleterious	D	0.532248681	None	None	N
E/H	0.5065	ambiguous	0.4836	ambiguous	-0.281	Destabilizing	0.999	D	0.741	deleterious	None	None	None	None	N
E/I	0.4193	ambiguous	0.413	ambiguous	0.111	Stabilizing	0.976	D	0.849	deleterious	None	None	None	None	N
E/K	0.1439	likely_benign	0.1356	benign	-0.088	Destabilizing	0.896	D	0.69	prob.neutral	D	0.531035172	None	None	N
E/L	0.4106	ambiguous	0.3955	ambiguous	0.111	Stabilizing	0.851	D	0.771	deleterious	None	None	None	None	N
E/M	0.5057	ambiguous	0.5039	ambiguous	0.296	Stabilizing	0.999	D	0.796	deleterious	None	None	None	None	N
E/N	0.3321	likely_benign	0.3214	benign	-0.417	Destabilizing	0.976	D	0.725	prob.delet.	None	None	None	None	N
E/P	0.5006	ambiguous	0.4618	ambiguous	-0.089	Destabilizing	0.988	D	0.741	deleterious	None	None	None	None	N
E/Q	0.1437	likely_benign	0.1429	benign	-0.357	Destabilizing	0.984	D	0.721	prob.delet.	N	0.512700128	None	None	N
E/R	0.2506	likely_benign	0.2353	benign	0.168	Stabilizing	0.976	D	0.719	prob.delet.	None	None	None	None	N
E/S	0.2322	likely_benign	0.2188	benign	-0.619	Destabilizing	0.851	D	0.703	prob.neutral	None	None	None	None	N
E/T	0.224	likely_benign	0.217	benign	-0.416	Destabilizing	0.132	N	0.536	neutral	None	None	None	None	N
E/V	0.2374	likely_benign	0.2334	benign	-0.089	Destabilizing	0.811	D	0.755	deleterious	D	0.532075322	None	None	N
E/W	0.8951	likely_pathogenic	0.8894	pathogenic	-0.113	Destabilizing	0.999	D	0.827	deleterious	None	None	None	None	N
E/Y	0.691	likely_pathogenic	0.6743	pathogenic	-0.061	Destabilizing	0.996	D	0.814	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.