TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27457	82594;82595;82596	chr2:178563763;178563762;178563761	chr2:179428490;179428489;179428488
N2AB	25816	77671;77672;77673	chr2:178563763;178563762;178563761	chr2:179428490;179428489;179428488
N2A	24889	74890;74891;74892	chr2:178563763;178563762;178563761	chr2:179428490;179428489;179428488
N2B	18392	55399;55400;55401	chr2:178563763;178563762;178563761	chr2:179428490;179428489;179428488
Novex-1	18517	55774;55775;55776	chr2:178563763;178563762;178563761	chr2:179428490;179428489;179428488
Novex-2	18584	55975;55976;55977	chr2:178563763;178563762;178563761	chr2:179428490;179428489;179428488
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: Fn3-87
• Domain position: 89
• Structural Position: 122
• Q(SASA): 0.3658
• 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	0.813	N	0.515	0.111	0.382925413656	gnomAD-4.0.0	1.36846E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79897E-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	0.2578	likely_benign	0.2872	benign	-0.75	Destabilizing	0.007	N	0.439	neutral	N	0.47486105	None	None	N
E/C	0.876	likely_pathogenic	0.8849	pathogenic	-0.378	Destabilizing	0.996	D	0.763	deleterious	None	None	None	None	N
E/D	0.2556	likely_benign	0.2367	benign	-0.926	Destabilizing	0.813	D	0.515	neutral	N	0.462224071	None	None	N
E/F	0.7883	likely_pathogenic	0.7951	pathogenic	0.17	Stabilizing	0.953	D	0.761	deleterious	None	None	None	None	N
E/G	0.453	ambiguous	0.473	ambiguous	-1.154	Destabilizing	0.518	D	0.576	neutral	N	0.494700052	None	None	N
E/H	0.6717	likely_pathogenic	0.6639	pathogenic	0.089	Stabilizing	0.996	D	0.52	neutral	None	None	None	None	N
E/I	0.3173	likely_benign	0.3557	ambiguous	0.368	Stabilizing	0.909	D	0.754	deleterious	None	None	None	None	N
E/K	0.3937	ambiguous	0.4042	ambiguous	-0.33	Destabilizing	0.682	D	0.439	neutral	N	0.47988748	None	None	N
E/L	0.3846	ambiguous	0.4211	ambiguous	0.368	Stabilizing	0.909	D	0.647	neutral	None	None	None	None	N
E/M	0.4902	ambiguous	0.5286	ambiguous	0.738	Stabilizing	0.996	D	0.719	prob.delet.	None	None	None	None	N
E/N	0.4897	ambiguous	0.4935	ambiguous	-1.042	Destabilizing	0.953	D	0.462	neutral	None	None	None	None	N
E/P	0.7967	likely_pathogenic	0.8247	pathogenic	0.016	Stabilizing	0.009	N	0.475	neutral	None	None	None	None	N
E/Q	0.2081	likely_benign	0.2121	benign	-0.864	Destabilizing	0.938	D	0.497	neutral	N	0.489196045	None	None	N
E/R	0.5511	ambiguous	0.5582	ambiguous	0.052	Stabilizing	0.953	D	0.464	neutral	None	None	None	None	N
E/S	0.3607	ambiguous	0.3788	ambiguous	-1.375	Destabilizing	0.587	D	0.417	neutral	None	None	None	None	N
E/T	0.2989	likely_benign	0.3288	benign	-1.019	Destabilizing	0.74	D	0.529	neutral	None	None	None	None	N
E/V	0.1867	likely_benign	0.2061	benign	0.016	Stabilizing	0.518	D	0.591	neutral	N	0.477622982	None	None	N
E/W	0.9484	likely_pathogenic	0.9456	pathogenic	0.541	Stabilizing	0.996	D	0.703	prob.delet.	None	None	None	None	N
E/Y	0.7441	likely_pathogenic	0.7351	pathogenic	0.486	Stabilizing	0.984	D	0.749	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.