TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8291	25096;25097;25098	chr2:178718135;178718134;178718133	chr2:179582862;179582861;179582860
N2AB	7974	24145;24146;24147	chr2:178718135;178718134;178718133	chr2:179582862;179582861;179582860
N2A	7047	21364;21365;21366	chr2:178718135;178718134;178718133	chr2:179582862;179582861;179582860
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: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Ig-68
• Domain position: 28
• Structural Position: 42
• Q(SASA): 0.6017
• Predicted PPI site: I

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
P/T	None	None	0.992	D	0.714	0.576	0.761910172549	gnomAD-4.0.0	1.60168E-06	None	None	None	None	I	None	0	0	None	0	0	None	2.03252E-05	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
P/A	0.7233	likely_pathogenic	0.8822	pathogenic	-0.578	Destabilizing	0.958	D	0.545	neutral	N	0.509282719	None	None	I
P/C	0.9916	likely_pathogenic	0.9971	pathogenic	-0.619	Destabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	I
P/D	0.9743	likely_pathogenic	0.9902	pathogenic	-0.42	Destabilizing	0.981	D	0.707	prob.neutral	None	None	None	None	I
P/E	0.9477	likely_pathogenic	0.9768	pathogenic	-0.542	Destabilizing	0.988	D	0.711	prob.delet.	None	None	None	None	I
P/F	0.9964	likely_pathogenic	0.9986	pathogenic	-0.806	Destabilizing	1.0	D	0.736	prob.delet.	None	None	None	None	I
P/G	0.8874	likely_pathogenic	0.9691	pathogenic	-0.711	Destabilizing	0.993	D	0.646	neutral	None	None	None	None	I
P/H	0.9688	likely_pathogenic	0.9887	pathogenic	-0.282	Destabilizing	1.0	D	0.695	prob.neutral	None	None	None	None	I
P/I	0.9858	likely_pathogenic	0.9915	pathogenic	-0.38	Destabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	I
P/K	0.9703	likely_pathogenic	0.9871	pathogenic	-0.522	Destabilizing	1.0	D	0.709	prob.delet.	None	None	None	None	I
P/L	0.9243	likely_pathogenic	0.9672	pathogenic	-0.38	Destabilizing	1.0	D	0.713	prob.delet.	D	0.588561966	None	None	I
P/M	0.98	likely_pathogenic	0.991	pathogenic	-0.363	Destabilizing	1.0	D	0.7	prob.neutral	None	None	None	None	I
P/N	0.9687	likely_pathogenic	0.9898	pathogenic	-0.224	Destabilizing	0.997	D	0.69	prob.neutral	None	None	None	None	I
P/Q	0.9382	likely_pathogenic	0.9751	pathogenic	-0.5	Destabilizing	0.999	D	0.714	prob.delet.	N	0.509282719	None	None	I
P/R	0.9359	likely_pathogenic	0.9709	pathogenic	0.037	Stabilizing	1.0	D	0.703	prob.neutral	D	0.581657748	None	None	I
P/S	0.8763	likely_pathogenic	0.9626	pathogenic	-0.575	Destabilizing	0.934	D	0.337	neutral	D	0.54103423	None	None	I
P/T	0.8405	likely_pathogenic	0.9288	pathogenic	-0.599	Destabilizing	0.992	D	0.714	prob.delet.	D	0.613696469	None	None	I
P/V	0.9551	likely_pathogenic	0.9728	pathogenic	-0.412	Destabilizing	0.999	D	0.694	prob.neutral	None	None	None	None	I
P/W	0.9974	likely_pathogenic	0.9988	pathogenic	-0.868	Destabilizing	1.0	D	0.73	prob.delet.	None	None	None	None	I
P/Y	0.9943	likely_pathogenic	0.9977	pathogenic	-0.58	Destabilizing	1.0	D	0.738	prob.delet.	None	None	None	None	I

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.