TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15578	46957;46958;46959	chr2:178618818;178618817;178618816	chr2:179483545;179483544;179483543
N2AB	13937	42034;42035;42036	chr2:178618818;178618817;178618816	chr2:179483545;179483544;179483543
N2A	13010	39253;39254;39255	chr2:178618818;178618817;178618816	chr2:179483545;179483544;179483543
N2B	6513	19762;19763;19764	chr2:178618818;178618817;178618816	chr2:179483545;179483544;179483543
Novex-1	6638	20137;20138;20139	chr2:178618818;178618817;178618816	chr2:179483545;179483544;179483543
Novex-2	6705	20338;20339;20340	chr2:178618818;178618817;178618816	chr2:179483545;179483544;179483543
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Ig-108
• Domain position: 11
• Structural Position: 14
• Q(SASA): 0.5401
• 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
V/A	None	None	0.999	N	0.496	0.431	0.656528602549	gnomAD-4.0.0	1.59845E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86668E-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
V/A	0.2441	likely_benign	0.2945	benign	-1.05	Destabilizing	0.999	D	0.496	neutral	N	0.508103218	None	None	N
V/C	0.792	likely_pathogenic	0.839	pathogenic	-0.841	Destabilizing	1.0	D	0.651	neutral	None	None	None	None	N
V/D	0.478	ambiguous	0.5097	ambiguous	-0.785	Destabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	N
V/E	0.3499	ambiguous	0.3694	ambiguous	-0.783	Destabilizing	1.0	D	0.714	prob.delet.	N	0.502448275	None	None	N
V/F	0.2412	likely_benign	0.2846	benign	-0.718	Destabilizing	1.0	D	0.711	prob.delet.	None	None	None	None	N
V/G	0.4273	ambiguous	0.4797	ambiguous	-1.342	Destabilizing	1.0	D	0.717	prob.delet.	N	0.512048216	None	None	N
V/H	0.6818	likely_pathogenic	0.7299	pathogenic	-0.765	Destabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	N
V/I	0.0809	likely_benign	0.0927	benign	-0.363	Destabilizing	0.998	D	0.473	neutral	None	None	None	None	N
V/K	0.5697	likely_pathogenic	0.6064	pathogenic	-0.999	Destabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	N
V/L	0.2441	likely_benign	0.3016	benign	-0.363	Destabilizing	0.997	D	0.486	neutral	N	0.51184647	None	None	N
V/M	0.1978	likely_benign	0.2625	benign	-0.445	Destabilizing	1.0	D	0.617	neutral	N	0.517110808	None	None	N
V/N	0.3831	ambiguous	0.4393	ambiguous	-0.854	Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	N
V/P	0.7526	likely_pathogenic	0.8095	pathogenic	-0.557	Destabilizing	1.0	D	0.712	prob.delet.	None	None	None	None	N
V/Q	0.4562	ambiguous	0.4773	ambiguous	-0.967	Destabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	N
V/R	0.5354	ambiguous	0.5538	ambiguous	-0.522	Destabilizing	1.0	D	0.738	prob.delet.	None	None	None	None	N
V/S	0.2907	likely_benign	0.3315	benign	-1.341	Destabilizing	1.0	D	0.716	prob.delet.	None	None	None	None	N
V/T	0.1761	likely_benign	0.2021	benign	-1.221	Destabilizing	0.999	D	0.607	neutral	None	None	None	None	N
V/W	0.8445	likely_pathogenic	0.8881	pathogenic	-0.898	Destabilizing	1.0	D	0.713	prob.delet.	None	None	None	None	N
V/Y	0.6202	likely_pathogenic	0.685	pathogenic	-0.597	Destabilizing	1.0	D	0.711	prob.delet.	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.