TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5058	15397;15398;15399	chr2:178734752;178734751;178734750	chr2:179599479;179599478;179599477
N2AB	4741	14446;14447;14448	chr2:178734752;178734751;178734750	chr2:179599479;179599478;179599477
N2A	3814	11665;11666;11667	chr2:178734752;178734751;178734750	chr2:179599479;179599478;179599477
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: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Ig-33
• Domain position: 78
• Structural Position: 161
• Q(SASA): 0.1468
• 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
N/S	rs773648136	-1.005	0.999	D	0.563	0.546	0.232513804876	gnomAD-2.1.1	8.04E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	1.78E-05	0
N/S	rs773648136	-1.005	0.999	D	0.563	0.546	0.232513804876	gnomAD-4.0.0	3.18528E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	5.72338E-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
N/A	0.9729	likely_pathogenic	0.979	pathogenic	-0.863	Destabilizing	1.0	D	0.736	prob.delet.	None	None	None	None	I
N/C	0.9257	likely_pathogenic	0.9379	pathogenic	-0.205	Destabilizing	1.0	D	0.676	prob.neutral	None	None	None	None	I
N/D	0.9111	likely_pathogenic	0.9127	pathogenic	-1.112	Destabilizing	0.999	D	0.595	neutral	D	0.709354663	None	None	I
N/E	0.994	likely_pathogenic	0.994	pathogenic	-1.051	Destabilizing	0.999	D	0.687	prob.neutral	None	None	None	None	I
N/F	0.9978	likely_pathogenic	0.9976	pathogenic	-0.855	Destabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	I
N/G	0.9326	likely_pathogenic	0.9386	pathogenic	-1.143	Destabilizing	0.999	D	0.536	neutral	None	None	None	None	I
N/H	0.94	likely_pathogenic	0.9446	pathogenic	-0.986	Destabilizing	1.0	D	0.722	prob.delet.	D	0.684128925	None	None	I
N/I	0.983	likely_pathogenic	0.9844	pathogenic	-0.17	Destabilizing	1.0	D	0.711	prob.delet.	D	0.767405593	None	None	I
N/K	0.9946	likely_pathogenic	0.995	pathogenic	-0.281	Destabilizing	1.0	D	0.705	prob.neutral	D	0.731731557	None	None	I
N/L	0.9508	likely_pathogenic	0.9531	pathogenic	-0.17	Destabilizing	1.0	D	0.713	prob.delet.	None	None	None	None	I
N/M	0.9719	likely_pathogenic	0.9758	pathogenic	0.376	Stabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	I
N/P	0.991	likely_pathogenic	0.9922	pathogenic	-0.374	Destabilizing	1.0	D	0.714	prob.delet.	None	None	None	None	I
N/Q	0.994	likely_pathogenic	0.994	pathogenic	-1.092	Destabilizing	1.0	D	0.714	prob.delet.	None	None	None	None	I
N/R	0.9929	likely_pathogenic	0.9928	pathogenic	-0.157	Destabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	I
N/S	0.4102	ambiguous	0.4605	ambiguous	-0.863	Destabilizing	0.999	D	0.563	neutral	D	0.571986437	None	None	I
N/T	0.7865	likely_pathogenic	0.8154	pathogenic	-0.639	Destabilizing	0.999	D	0.677	prob.neutral	D	0.662833165	None	None	I
N/V	0.9769	likely_pathogenic	0.9801	pathogenic	-0.374	Destabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	I
N/W	0.9988	likely_pathogenic	0.9988	pathogenic	-0.629	Destabilizing	1.0	D	0.672	neutral	None	None	None	None	I
N/Y	0.9775	likely_pathogenic	0.9776	pathogenic	-0.388	Destabilizing	1.0	D	0.726	prob.delet.	D	0.766670733	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.