TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30143	90652;90653;90654	chr2:178552473;178552472;178552471	chr2:179417200;179417199;179417198
N2AB	28502	85729;85730;85731	chr2:178552473;178552472;178552471	chr2:179417200;179417199;179417198
N2A	27575	82948;82949;82950	chr2:178552473;178552472;178552471	chr2:179417200;179417199;179417198
N2B	21078	63457;63458;63459	chr2:178552473;178552472;178552471	chr2:179417200;179417199;179417198
Novex-1	21203	63832;63833;63834	chr2:178552473;178552472;178552471	chr2:179417200;179417199;179417198
Novex-2	21270	64033;64034;64035	chr2:178552473;178552472;178552471	chr2:179417200;179417199;179417198
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Ig-148
• Domain position: 12
• Structural Position: 16
• Q(SASA): 0.3861
• 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
V/L	rs1287481084	-0.312	0.997	D	0.502	0.526	0.741963092889	gnomAD-2.1.1	4.04E-06	None	None	None	None	I	None	6.46E-05	0	None	0	0	None	0	None	0	0	0
V/L	rs1287481084	-0.312	0.997	D	0.502	0.526	0.741963092889	gnomAD-4.0.0	6.85653E-07	None	None	None	None	I	None	2.99168E-05	0	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
V/A	0.3962	ambiguous	0.3434	ambiguous	-1.1	Destabilizing	0.999	D	0.466	neutral	N	0.468608208	None	None	I
V/C	0.8563	likely_pathogenic	0.8123	pathogenic	-0.741	Destabilizing	1.0	D	0.656	neutral	None	None	None	None	I
V/D	0.9685	likely_pathogenic	0.9522	pathogenic	-0.655	Destabilizing	1.0	D	0.703	prob.neutral	None	None	None	None	I
V/E	0.9073	likely_pathogenic	0.8704	pathogenic	-0.706	Destabilizing	1.0	D	0.66	neutral	N	0.517735281	None	None	I
V/F	0.622	likely_pathogenic	0.5516	ambiguous	-0.987	Destabilizing	1.0	D	0.701	prob.neutral	None	None	None	None	I
V/G	0.6297	likely_pathogenic	0.5617	ambiguous	-1.354	Destabilizing	1.0	D	0.688	prob.neutral	N	0.512708851	None	None	I
V/H	0.9708	likely_pathogenic	0.9532	pathogenic	-0.947	Destabilizing	1.0	D	0.666	neutral	None	None	None	None	I
V/I	0.1106	likely_benign	0.1064	benign	-0.536	Destabilizing	0.998	D	0.509	neutral	None	None	None	None	I
V/K	0.9226	likely_pathogenic	0.8854	pathogenic	-0.908	Destabilizing	1.0	D	0.655	neutral	None	None	None	None	I
V/L	0.5361	ambiguous	0.4648	ambiguous	-0.536	Destabilizing	0.997	D	0.502	neutral	D	0.537508146	None	None	I
V/M	0.3877	ambiguous	0.3228	benign	-0.407	Destabilizing	1.0	D	0.741	deleterious	N	0.517228302	None	None	I
V/N	0.8963	likely_pathogenic	0.859	pathogenic	-0.604	Destabilizing	1.0	D	0.697	prob.neutral	None	None	None	None	I
V/P	0.98	likely_pathogenic	0.978	pathogenic	-0.688	Destabilizing	1.0	D	0.669	neutral	None	None	None	None	I
V/Q	0.8677	likely_pathogenic	0.8183	pathogenic	-0.799	Destabilizing	1.0	D	0.673	neutral	None	None	None	None	I
V/R	0.8962	likely_pathogenic	0.856	pathogenic	-0.412	Destabilizing	1.0	D	0.693	prob.neutral	None	None	None	None	I
V/S	0.6477	likely_pathogenic	0.5736	pathogenic	-1.087	Destabilizing	1.0	D	0.667	neutral	None	None	None	None	I
V/T	0.4773	ambiguous	0.3971	ambiguous	-1.029	Destabilizing	0.999	D	0.646	neutral	None	None	None	None	I
V/W	0.991	likely_pathogenic	0.9856	pathogenic	-1.125	Destabilizing	1.0	D	0.659	neutral	None	None	None	None	I
V/Y	0.9472	likely_pathogenic	0.921	pathogenic	-0.833	Destabilizing	1.0	D	0.705	prob.neutral	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.