TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25033	75322;75323;75324	chr2:178571035;178571034;178571033	chr2:179435762;179435761;179435760
N2AB	23392	70399;70400;70401	chr2:178571035;178571034;178571033	chr2:179435762;179435761;179435760
N2A	22465	67618;67619;67620	chr2:178571035;178571034;178571033	chr2:179435762;179435761;179435760
N2B	15968	48127;48128;48129	chr2:178571035;178571034;178571033	chr2:179435762;179435761;179435760
Novex-1	16093	48502;48503;48504	chr2:178571035;178571034;178571033	chr2:179435762;179435761;179435760
Novex-2	16160	48703;48704;48705	chr2:178571035;178571034;178571033	chr2:179435762;179435761;179435760
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAC
• RefSeq wild type template codon: CTG
• Domain: Fn3-70
• Domain position: 28
• Structural Position: 30
• Q(SASA): 0.1934
• 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
D/E	None	None	1.0	N	0.452	0.39	0.366085729538	gnomAD-4.0.0	1.36964E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.80057E-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
D/A	0.7878	likely_pathogenic	0.7983	pathogenic	-0.529	Destabilizing	1.0	D	0.747	deleterious	N	0.498324584	None	None	I
D/C	0.9402	likely_pathogenic	0.9437	pathogenic	-0.186	Destabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	I
D/E	0.7611	likely_pathogenic	0.7658	pathogenic	-0.798	Destabilizing	1.0	D	0.452	neutral	N	0.493525191	None	None	I
D/F	0.9676	likely_pathogenic	0.9732	pathogenic	-0.628	Destabilizing	1.0	D	0.744	deleterious	None	None	None	None	I
D/G	0.7906	likely_pathogenic	0.7939	pathogenic	-0.842	Destabilizing	1.0	D	0.707	prob.neutral	N	0.521735211	None	None	I
D/H	0.8689	likely_pathogenic	0.8702	pathogenic	-1.057	Destabilizing	1.0	D	0.717	prob.delet.	N	0.513239288	None	None	I
D/I	0.9345	likely_pathogenic	0.9435	pathogenic	0.286	Stabilizing	1.0	D	0.759	deleterious	None	None	None	None	I
D/K	0.9593	likely_pathogenic	0.9598	pathogenic	-0.414	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	I
D/L	0.92	likely_pathogenic	0.9348	pathogenic	0.286	Stabilizing	1.0	D	0.764	deleterious	None	None	None	None	I
D/M	0.9661	likely_pathogenic	0.971	pathogenic	0.842	Stabilizing	1.0	D	0.728	prob.delet.	None	None	None	None	I
D/N	0.2027	likely_benign	0.2277	benign	-0.735	Destabilizing	1.0	D	0.708	prob.delet.	N	0.511998334	None	None	I
D/P	0.9765	likely_pathogenic	0.9772	pathogenic	0.039	Stabilizing	1.0	D	0.777	deleterious	None	None	None	None	I
D/Q	0.919	likely_pathogenic	0.9181	pathogenic	-0.614	Destabilizing	1.0	D	0.767	deleterious	None	None	None	None	I
D/R	0.9477	likely_pathogenic	0.9474	pathogenic	-0.462	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	I
D/S	0.3933	ambiguous	0.4141	ambiguous	-0.989	Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	I
D/T	0.5553	ambiguous	0.5995	pathogenic	-0.726	Destabilizing	1.0	D	0.77	deleterious	None	None	None	None	I
D/V	0.8485	likely_pathogenic	0.8655	pathogenic	0.039	Stabilizing	1.0	D	0.767	deleterious	N	0.512732309	None	None	I
D/W	0.9934	likely_pathogenic	0.9938	pathogenic	-0.62	Destabilizing	1.0	D	0.723	prob.delet.	None	None	None	None	I
D/Y	0.8298	likely_pathogenic	0.8416	pathogenic	-0.433	Destabilizing	1.0	D	0.727	prob.delet.	D	0.548233257	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.