TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28499	85720;85721;85722	chr2:178560637;178560636;178560635	chr2:179425364;179425363;179425362
N2AB	26858	80797;80798;80799	chr2:178560637;178560636;178560635	chr2:179425364;179425363;179425362
N2A	25931	78016;78017;78018	chr2:178560637;178560636;178560635	chr2:179425364;179425363;179425362
N2B	19434	58525;58526;58527	chr2:178560637;178560636;178560635	chr2:179425364;179425363;179425362
Novex-1	19559	58900;58901;58902	chr2:178560637;178560636;178560635	chr2:179425364;179425363;179425362
Novex-2	19626	59101;59102;59103	chr2:178560637;178560636;178560635	chr2:179425364;179425363;179425362
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Fn3-95
• Domain position: 50
• Structural Position: 66
• Q(SASA): 0.365
• 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
T/K	rs1703270570	None	0.988	N	0.677	0.437	0.561103792788	gnomAD-4.0.0	6.84306E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	1.7337E-04	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
T/A	0.1251	likely_benign	0.1304	benign	-0.593	Destabilizing	0.067	N	0.258	neutral	D	0.5226739	None	None	I
T/C	0.5872	likely_pathogenic	0.633	pathogenic	-0.406	Destabilizing	0.999	D	0.715	prob.delet.	None	None	None	None	I
T/D	0.5453	ambiguous	0.599	pathogenic	0.171	Stabilizing	0.995	D	0.727	prob.delet.	None	None	None	None	I
T/E	0.4053	ambiguous	0.4626	ambiguous	0.149	Stabilizing	0.991	D	0.687	prob.neutral	None	None	None	None	I
T/F	0.3876	ambiguous	0.4264	ambiguous	-0.764	Destabilizing	0.995	D	0.729	prob.delet.	None	None	None	None	I
T/G	0.3794	ambiguous	0.4077	ambiguous	-0.813	Destabilizing	0.938	D	0.597	neutral	None	None	None	None	I
T/H	0.2842	likely_benign	0.3156	benign	-1.003	Destabilizing	1.0	D	0.72	prob.delet.	None	None	None	None	I
T/I	0.2295	likely_benign	0.2625	benign	-0.114	Destabilizing	0.988	D	0.729	prob.delet.	N	0.503800138	None	None	I
T/K	0.2356	likely_benign	0.2611	benign	-0.57	Destabilizing	0.988	D	0.677	prob.neutral	N	0.467263727	None	None	I
T/L	0.1483	likely_benign	0.1634	benign	-0.114	Destabilizing	0.938	D	0.575	neutral	None	None	None	None	I
T/M	0.0987	likely_benign	0.0995	benign	-0.036	Destabilizing	1.0	D	0.723	prob.delet.	None	None	None	None	I
T/N	0.1411	likely_benign	0.155	benign	-0.444	Destabilizing	0.995	D	0.701	prob.neutral	None	None	None	None	I
T/P	0.5682	likely_pathogenic	0.6339	pathogenic	-0.242	Destabilizing	0.994	D	0.731	prob.delet.	N	0.510059283	None	None	I
T/Q	0.2462	likely_benign	0.2677	benign	-0.585	Destabilizing	0.995	D	0.725	prob.delet.	None	None	None	None	I
T/R	0.1819	likely_benign	0.1993	benign	-0.314	Destabilizing	0.994	D	0.717	prob.delet.	N	0.511264828	None	None	I
T/S	0.1534	likely_benign	0.1671	benign	-0.719	Destabilizing	0.919	D	0.484	neutral	N	0.511611545	None	None	I
T/V	0.1718	likely_benign	0.1942	benign	-0.242	Destabilizing	0.938	D	0.535	neutral	None	None	None	None	I
T/W	0.7148	likely_pathogenic	0.7443	pathogenic	-0.738	Destabilizing	1.0	D	0.74	deleterious	None	None	None	None	I
T/Y	0.3729	ambiguous	0.4212	ambiguous	-0.491	Destabilizing	0.998	D	0.728	prob.delet.	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.