TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28237	84934;84935;84936	chr2:178561423;178561422;178561421	chr2:179426150;179426149;179426148
N2AB	26596	80011;80012;80013	chr2:178561423;178561422;178561421	chr2:179426150;179426149;179426148
N2A	25669	77230;77231;77232	chr2:178561423;178561422;178561421	chr2:179426150;179426149;179426148
N2B	19172	57739;57740;57741	chr2:178561423;178561422;178561421	chr2:179426150;179426149;179426148
Novex-1	19297	58114;58115;58116	chr2:178561423;178561422;178561421	chr2:179426150;179426149;179426148
Novex-2	19364	58315;58316;58317	chr2:178561423;178561422;178561421	chr2:179426150;179426149;179426148
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: Fn3-93
• Domain position: 84
• Structural Position: 117
• Q(SASA): 0.3213
• 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
I/M	rs1703616150	None	0.971	N	0.724	0.244	0.343101102393	gnomAD-4.0.0	2.73681E-06	None	None	None	None	I	None	2.98793E-05	6.70811E-05	None	0	0	None	0	0	0	0	0
I/S	rs1479599357	-1.622	0.698	N	0.75	0.33	0.663906303568	gnomAD-4.0.0	1.59123E-06	None	None	None	None	I	None	0	2.28634E-05	None	0	0	None	0	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
I/A	0.2296	likely_benign	0.2206	benign	-1.357	Destabilizing	0.754	D	0.633	neutral	None	None	None	None	I
I/C	0.6744	likely_pathogenic	0.6691	pathogenic	-0.838	Destabilizing	0.998	D	0.748	deleterious	None	None	None	None	I
I/D	0.8603	likely_pathogenic	0.8245	pathogenic	-0.629	Destabilizing	0.956	D	0.816	deleterious	None	None	None	None	I
I/E	0.6973	likely_pathogenic	0.6756	pathogenic	-0.661	Destabilizing	0.956	D	0.813	deleterious	None	None	None	None	I
I/F	0.2088	likely_benign	0.2021	benign	-1.013	Destabilizing	0.971	D	0.721	prob.delet.	N	0.491348129	None	None	I
I/G	0.7297	likely_pathogenic	0.6917	pathogenic	-1.632	Destabilizing	0.956	D	0.797	deleterious	None	None	None	None	I
I/H	0.6732	likely_pathogenic	0.6469	pathogenic	-0.732	Destabilizing	0.998	D	0.818	deleterious	None	None	None	None	I
I/K	0.4412	ambiguous	0.4361	ambiguous	-0.796	Destabilizing	0.956	D	0.814	deleterious	None	None	None	None	I
I/L	0.1299	likely_benign	0.1307	benign	-0.699	Destabilizing	0.489	N	0.392	neutral	N	0.448287998	None	None	I
I/M	0.1199	likely_benign	0.1201	benign	-0.582	Destabilizing	0.971	D	0.724	prob.delet.	N	0.486846386	None	None	I
I/N	0.4875	ambiguous	0.4426	ambiguous	-0.559	Destabilizing	0.942	D	0.82	deleterious	N	0.468843435	None	None	I
I/P	0.5792	likely_pathogenic	0.5332	ambiguous	-0.885	Destabilizing	0.978	D	0.823	deleterious	None	None	None	None	I
I/Q	0.5554	ambiguous	0.537	ambiguous	-0.77	Destabilizing	0.978	D	0.824	deleterious	None	None	None	None	I
I/R	0.3555	ambiguous	0.3468	ambiguous	-0.167	Destabilizing	0.956	D	0.819	deleterious	None	None	None	None	I
I/S	0.3522	ambiguous	0.3239	benign	-1.157	Destabilizing	0.698	D	0.75	deleterious	N	0.520457527	None	None	I
I/T	0.107	likely_benign	0.109	benign	-1.068	Destabilizing	0.014	N	0.437	neutral	N	0.502045125	None	None	I
I/V	0.0669	likely_benign	0.0682	benign	-0.885	Destabilizing	0.294	N	0.358	neutral	N	0.454117892	None	None	I
I/W	0.8303	likely_pathogenic	0.8179	pathogenic	-1.006	Destabilizing	0.998	D	0.796	deleterious	None	None	None	None	I
I/Y	0.6383	likely_pathogenic	0.6189	pathogenic	-0.796	Destabilizing	0.993	D	0.753	deleterious	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.