TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7725	23398;23399;23400	chr2:178720589;178720588;178720587	chr2:179585316;179585315;179585314
N2AB	7408	22447;22448;22449	chr2:178720589;178720588;178720587	chr2:179585316;179585315;179585314
N2A	6481	19666;19667;19668	chr2:178720589;178720588;178720587	chr2:179585316;179585315;179585314
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: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Ig-62
• Domain position: 24
• Structural Position: 35
• Q(SASA): 0.11
• 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
I/M	rs1270184889	None	0.81	N	0.673	0.362	0.449669948863	gnomAD-4.0.0	1.59241E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85999E-06	0	0
I/T	None	None	0.549	N	0.669	0.423	0.631214040921	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
I/A	0.9119	likely_pathogenic	0.9074	pathogenic	-2.541	Highly Destabilizing	0.009	N	0.405	neutral	None	None	None	None	N
I/C	0.951	likely_pathogenic	0.9502	pathogenic	-1.959	Destabilizing	0.992	D	0.739	prob.delet.	None	None	None	None	N
I/D	0.9972	likely_pathogenic	0.9967	pathogenic	-2.801	Highly Destabilizing	0.92	D	0.813	deleterious	None	None	None	None	N
I/E	0.9937	likely_pathogenic	0.993	pathogenic	-2.545	Highly Destabilizing	0.92	D	0.795	deleterious	None	None	None	None	N
I/F	0.4218	ambiguous	0.4062	ambiguous	-1.458	Destabilizing	0.681	D	0.703	prob.neutral	N	0.498200396	None	None	N
I/G	0.9857	likely_pathogenic	0.9837	pathogenic	-3.089	Highly Destabilizing	0.617	D	0.761	deleterious	None	None	None	None	N
I/H	0.9859	likely_pathogenic	0.9851	pathogenic	-2.575	Highly Destabilizing	0.992	D	0.785	deleterious	None	None	None	None	N
I/K	0.9835	likely_pathogenic	0.9817	pathogenic	-1.662	Destabilizing	0.92	D	0.785	deleterious	None	None	None	None	N
I/L	0.1259	likely_benign	0.1162	benign	-0.931	Destabilizing	0.001	N	0.187	neutral	N	0.444539269	None	None	N
I/M	0.2155	likely_benign	0.2043	benign	-1.171	Destabilizing	0.81	D	0.673	neutral	N	0.501842617	None	None	N
I/N	0.9575	likely_pathogenic	0.9477	pathogenic	-2.098	Highly Destabilizing	0.963	D	0.813	deleterious	N	0.502349596	None	None	N
I/P	0.9932	likely_pathogenic	0.9923	pathogenic	-1.452	Destabilizing	0.92	D	0.813	deleterious	None	None	None	None	N
I/Q	0.9858	likely_pathogenic	0.9846	pathogenic	-1.897	Destabilizing	0.972	D	0.813	deleterious	None	None	None	None	N
I/R	0.9765	likely_pathogenic	0.9746	pathogenic	-1.564	Destabilizing	0.92	D	0.814	deleterious	None	None	None	None	N
I/S	0.959	likely_pathogenic	0.9539	pathogenic	-2.789	Highly Destabilizing	0.379	N	0.713	prob.delet.	N	0.479961352	None	None	N
I/T	0.913	likely_pathogenic	0.9057	pathogenic	-2.383	Highly Destabilizing	0.549	D	0.669	neutral	N	0.496429527	None	None	N
I/V	0.139	likely_benign	0.1357	benign	-1.452	Destabilizing	0.007	N	0.169	neutral	N	0.363757752	None	None	N
I/W	0.9815	likely_pathogenic	0.9803	pathogenic	-1.792	Destabilizing	0.992	D	0.771	deleterious	None	None	None	None	N
I/Y	0.9042	likely_pathogenic	0.8925	pathogenic	-1.549	Destabilizing	0.92	D	0.777	deleterious	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.