TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9603	29032;29033;29034	chr2:178707760;178707759;178707758	chr2:179572487;179572486;179572485
N2AB	9286	28081;28082;28083	chr2:178707760;178707759;178707758	chr2:179572487;179572486;179572485
N2A	8359	25300;25301;25302	chr2:178707760;178707759;178707758	chr2:179572487;179572486;179572485
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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-82
• Domain position: 14
• Structural Position: 23
• Q(SASA): 0.6222
• 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/G	None	None	0.999	None	0.646	0.32	0.346085882481	gnomAD-4.0.0	1.59134E-06	None	None	None	None	N	None	0	0	None	0	2.77269E-05	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	0.1571	likely_benign	0.1392	benign	-0.716	Destabilizing	0.998	D	0.639	neutral	None	None	None	None	N
E/C	0.9236	likely_pathogenic	0.9004	pathogenic	-0.171	Destabilizing	1.0	D	0.804	deleterious	None	None	None	None	N
E/D	0.2074	likely_benign	0.2046	benign	-0.601	Destabilizing	0.434	N	0.269	neutral	None	None	None	None	N
E/F	0.8683	likely_pathogenic	0.8131	pathogenic	-0.401	Destabilizing	1.0	D	0.758	deleterious	None	None	None	None	N
E/G	0.2343	likely_benign	0.1916	benign	-0.978	Destabilizing	0.999	D	0.646	neutral	None	None	None	None	N
E/H	0.6182	likely_pathogenic	0.5504	ambiguous	-0.37	Destabilizing	1.0	D	0.691	prob.neutral	None	None	None	None	N
E/I	0.4813	ambiguous	0.4015	ambiguous	-0.033	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
E/K	0.1816	likely_benign	0.1407	benign	0.096	Stabilizing	0.998	D	0.579	neutral	None	None	None	None	N
E/L	0.5176	ambiguous	0.4252	ambiguous	-0.033	Destabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	N
E/M	0.5938	likely_pathogenic	0.5005	ambiguous	0.245	Stabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	N
E/N	0.3881	ambiguous	0.3492	ambiguous	-0.373	Destabilizing	0.999	D	0.709	prob.delet.	None	None	None	None	N
E/P	0.5074	ambiguous	0.5106	ambiguous	-0.241	Destabilizing	1.0	D	0.688	prob.neutral	None	None	None	None	N
E/Q	0.181	likely_benign	0.1513	benign	-0.312	Destabilizing	0.999	D	0.655	neutral	None	None	None	None	N
E/R	0.3372	likely_benign	0.2631	benign	0.313	Stabilizing	1.0	D	0.699	prob.neutral	None	None	None	None	N
E/S	0.2504	likely_benign	0.2248	benign	-0.561	Destabilizing	0.997	D	0.614	neutral	None	None	None	None	N
E/T	0.3037	likely_benign	0.2604	benign	-0.34	Destabilizing	1.0	D	0.671	neutral	None	None	None	None	N
E/V	0.2842	likely_benign	0.2294	benign	-0.241	Destabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	N
E/W	0.9597	likely_pathogenic	0.932	pathogenic	-0.147	Destabilizing	1.0	D	0.81	deleterious	None	None	None	None	N
E/Y	0.7952	likely_pathogenic	0.729	pathogenic	-0.131	Destabilizing	1.0	D	0.743	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.