TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1337	4234;4235;4236	chr2:178779073;178779072;178779071	chr2:179643800;179643799;179643798
N2AB	1337	4234;4235;4236	chr2:178779073;178779072;178779071	chr2:179643800;179643799;179643798
N2A	1337	4234;4235;4236	chr2:178779073;178779072;178779071	chr2:179643800;179643799;179643798
N2B	1291	4096;4097;4098	chr2:178779073;178779072;178779071	chr2:179643800;179643799;179643798
Novex-1	1291	4096;4097;4098	chr2:178779073;178779072;178779071	chr2:179643800;179643799;179643798
Novex-2	1291	4096;4097;4098	chr2:178779073;178779072;178779071	chr2:179643800;179643799;179643798
Novex-3	1337	4234;4235;4236	chr2:178779073;178779072;178779071	chr2:179643800;179643799;179643798

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAC
• RefSeq wild type template codon: ATG
• Domain: Ig-5
• Domain position: 47
• Structural Position: 121
• Q(SASA): 0.174
• 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
Y/H	None	None	0.059	N	0.384	0.411	0.336400405673	gnomAD-4.0.0	1.20033E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.31251E-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
Y/A	0.9877	likely_pathogenic	0.9895	pathogenic	-2.783	Highly Destabilizing	0.919	D	0.657	neutral	None	None	None	None	N
Y/C	0.7949	likely_pathogenic	0.8403	pathogenic	-1.801	Destabilizing	0.999	D	0.73	prob.delet.	D	0.581627927	None	None	N
Y/D	0.9903	likely_pathogenic	0.9898	pathogenic	-2.266	Highly Destabilizing	0.938	D	0.74	deleterious	D	0.675575731	None	None	N
Y/E	0.9954	likely_pathogenic	0.9953	pathogenic	-2.1	Highly Destabilizing	0.976	D	0.695	prob.neutral	None	None	None	None	N
Y/F	0.1999	likely_benign	0.2077	benign	-1.078	Destabilizing	0.026	N	0.368	neutral	N	0.507230402	None	None	N
Y/G	0.9701	likely_pathogenic	0.9748	pathogenic	-3.187	Highly Destabilizing	0.919	D	0.703	prob.neutral	None	None	None	None	N
Y/H	0.8691	likely_pathogenic	0.9044	pathogenic	-1.694	Destabilizing	0.059	N	0.384	neutral	N	0.512558387	None	None	N
Y/I	0.9499	likely_pathogenic	0.9427	pathogenic	-1.487	Destabilizing	0.952	D	0.706	prob.neutral	None	None	None	None	N
Y/K	0.994	likely_pathogenic	0.9946	pathogenic	-2.061	Highly Destabilizing	0.976	D	0.706	prob.neutral	None	None	None	None	N
Y/L	0.9248	likely_pathogenic	0.9222	pathogenic	-1.487	Destabilizing	0.851	D	0.607	neutral	None	None	None	None	N
Y/M	0.976	likely_pathogenic	0.9752	pathogenic	-1.265	Destabilizing	0.997	D	0.696	prob.neutral	None	None	None	None	N
Y/N	0.9415	likely_pathogenic	0.9443	pathogenic	-2.666	Highly Destabilizing	0.211	N	0.487	neutral	D	0.635526245	None	None	N
Y/P	0.996	likely_pathogenic	0.9957	pathogenic	-1.925	Destabilizing	0.996	D	0.798	deleterious	None	None	None	None	N
Y/Q	0.9917	likely_pathogenic	0.993	pathogenic	-2.436	Highly Destabilizing	0.976	D	0.743	deleterious	None	None	None	None	N
Y/R	0.9815	likely_pathogenic	0.9842	pathogenic	-1.792	Destabilizing	0.976	D	0.723	prob.delet.	None	None	None	None	N
Y/S	0.9621	likely_pathogenic	0.9678	pathogenic	-3.147	Highly Destabilizing	0.896	D	0.677	prob.neutral	N	0.507214285	None	None	N
Y/T	0.9842	likely_pathogenic	0.9857	pathogenic	-2.862	Highly Destabilizing	0.976	D	0.701	prob.neutral	None	None	None	None	N
Y/V	0.9191	likely_pathogenic	0.9162	pathogenic	-1.925	Destabilizing	0.919	D	0.655	neutral	None	None	None	None	N
Y/W	0.7668	likely_pathogenic	0.792	pathogenic	-0.515	Destabilizing	0.999	D	0.642	neutral	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.