TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20990	63193;63194;63195	chr2:178588757;178588756;178588755	chr2:179453484;179453483;179453482
N2AB	19349	58270;58271;58272	chr2:178588757;178588756;178588755	chr2:179453484;179453483;179453482
N2A	18422	55489;55490;55491	chr2:178588757;178588756;178588755	chr2:179453484;179453483;179453482
N2B	11925	35998;35999;36000	chr2:178588757;178588756;178588755	chr2:179453484;179453483;179453482
Novex-1	12050	36373;36374;36375	chr2:178588757;178588756;178588755	chr2:179453484;179453483;179453482
Novex-2	12117	36574;36575;36576	chr2:178588757;178588756;178588755	chr2:179453484;179453483;179453482
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Fn3-40
• Domain position: 28
• Structural Position: 30
• Q(SASA): 0.1938
• 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
D/V	rs1466596917	-0.125	1.0	N	0.783	0.529	0.731595734459	gnomAD-2.1.1	1.21E-05	None	None	None	None	N	None	0	0	None	0	1.68199E-04	None	0	None	0	0	0
D/V	rs1466596917	-0.125	1.0	N	0.783	0.529	0.731595734459	gnomAD-4.0.0	6.3688E-06	None	None	None	None	N	None	0	0	None	0	1.11259E-04	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
D/A	0.8649	likely_pathogenic	0.8512	pathogenic	-0.768	Destabilizing	1.0	D	0.749	deleterious	N	0.495855822	None	None	N
D/C	0.964	likely_pathogenic	0.9601	pathogenic	-0.275	Destabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	N
D/E	0.8655	likely_pathogenic	0.8614	pathogenic	-0.642	Destabilizing	1.0	D	0.483	neutral	N	0.483485559	None	None	N
D/F	0.9845	likely_pathogenic	0.9841	pathogenic	-0.449	Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	N
D/G	0.8119	likely_pathogenic	0.8096	pathogenic	-1.117	Destabilizing	1.0	D	0.723	prob.delet.	N	0.506593471	None	None	N
D/H	0.9001	likely_pathogenic	0.8932	pathogenic	-0.801	Destabilizing	1.0	D	0.716	prob.delet.	N	0.505833002	None	None	N
D/I	0.9642	likely_pathogenic	0.9614	pathogenic	0.159	Stabilizing	1.0	D	0.773	deleterious	None	None	None	None	N
D/K	0.9647	likely_pathogenic	0.9584	pathogenic	-0.378	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
D/L	0.9514	likely_pathogenic	0.9462	pathogenic	0.159	Stabilizing	1.0	D	0.779	deleterious	None	None	None	None	N
D/M	0.984	likely_pathogenic	0.9821	pathogenic	0.678	Stabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	N
D/N	0.2517	likely_benign	0.2503	benign	-0.794	Destabilizing	1.0	D	0.685	prob.neutral	N	0.51523064	None	None	N
D/P	0.9703	likely_pathogenic	0.9628	pathogenic	-0.126	Destabilizing	1.0	D	0.788	deleterious	None	None	None	None	N
D/Q	0.9475	likely_pathogenic	0.9395	pathogenic	-0.664	Destabilizing	1.0	D	0.749	deleterious	None	None	None	None	N
D/R	0.9537	likely_pathogenic	0.946	pathogenic	-0.299	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
D/S	0.4994	ambiguous	0.4855	ambiguous	-1.091	Destabilizing	1.0	D	0.711	prob.delet.	None	None	None	None	N
D/T	0.7077	likely_pathogenic	0.6974	pathogenic	-0.794	Destabilizing	1.0	D	0.786	deleterious	None	None	None	None	N
D/V	0.9105	likely_pathogenic	0.9048	pathogenic	-0.126	Destabilizing	1.0	D	0.783	deleterious	N	0.513061478	None	None	N
D/W	0.9959	likely_pathogenic	0.9958	pathogenic	-0.249	Destabilizing	1.0	D	0.726	prob.delet.	None	None	None	None	N
D/Y	0.8876	likely_pathogenic	0.8744	pathogenic	-0.192	Destabilizing	1.0	D	0.73	prob.delet.	D	0.540826971	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.