TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18641	56146;56147;56148	chr2:178600983;178600982;178600981	chr2:179465710;179465709;179465708
N2AB	17000	51223;51224;51225	chr2:178600983;178600982;178600981	chr2:179465710;179465709;179465708
N2A	16073	48442;48443;48444	chr2:178600983;178600982;178600981	chr2:179465710;179465709;179465708
N2B	9576	28951;28952;28953	chr2:178600983;178600982;178600981	chr2:179465710;179465709;179465708
Novex-1	9701	29326;29327;29328	chr2:178600983;178600982;178600981	chr2:179465710;179465709;179465708
Novex-2	9768	29527;29528;29529	chr2:178600983;178600982;178600981	chr2:179465710;179465709;179465708
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-23
• Domain position: 63
• Structural Position: 88
• Q(SASA): 0.3335
• 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
E/K	None	None	0.581	N	0.577	0.182	0.284539287134	gnomAD-4.0.0	6.84482E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.15982E-05	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
E/A	0.1383	likely_benign	0.1203	benign	-0.232	Destabilizing	0.581	D	0.649	neutral	N	0.474344022	None	None	N
E/C	0.8114	likely_pathogenic	0.7444	pathogenic	-0.384	Destabilizing	0.993	D	0.722	prob.delet.	None	None	None	None	N
E/D	0.0953	likely_benign	0.0776	benign	-0.758	Destabilizing	0.004	N	0.204	neutral	N	0.45648898	None	None	N
E/F	0.6948	likely_pathogenic	0.6178	pathogenic	0.409	Stabilizing	0.993	D	0.731	prob.delet.	None	None	None	None	N
E/G	0.127	likely_benign	0.1042	benign	-0.542	Destabilizing	0.83	D	0.663	neutral	N	0.458259849	None	None	N
E/H	0.4618	ambiguous	0.3941	ambiguous	0.641	Stabilizing	0.98	D	0.683	prob.neutral	None	None	None	None	N
E/I	0.3687	ambiguous	0.3107	benign	0.591	Stabilizing	0.929	D	0.765	deleterious	None	None	None	None	N
E/K	0.1907	likely_benign	0.1704	benign	0.067	Stabilizing	0.581	D	0.577	neutral	N	0.477229612	None	None	N
E/L	0.4065	ambiguous	0.3237	benign	0.591	Stabilizing	0.866	D	0.761	deleterious	None	None	None	None	N
E/M	0.4391	ambiguous	0.3652	ambiguous	0.483	Stabilizing	0.993	D	0.711	prob.delet.	None	None	None	None	N
E/N	0.1622	likely_benign	0.1269	benign	-0.644	Destabilizing	0.764	D	0.696	prob.neutral	None	None	None	None	N
E/P	0.712	likely_pathogenic	0.6859	pathogenic	0.339	Stabilizing	0.929	D	0.77	deleterious	None	None	None	None	N
E/Q	0.1743	likely_benign	0.1475	benign	-0.495	Destabilizing	0.83	D	0.633	neutral	N	0.469399563	None	None	N
E/R	0.3203	likely_benign	0.2928	benign	0.486	Stabilizing	0.866	D	0.716	prob.delet.	None	None	None	None	N
E/S	0.17	likely_benign	0.1407	benign	-0.806	Destabilizing	0.48	N	0.615	neutral	None	None	None	None	N
E/T	0.1799	likely_benign	0.1464	benign	-0.53	Destabilizing	0.866	D	0.726	prob.delet.	None	None	None	None	N
E/V	0.2163	likely_benign	0.1843	benign	0.339	Stabilizing	0.908	D	0.744	deleterious	N	0.475402815	None	None	N
E/W	0.8979	likely_pathogenic	0.8532	pathogenic	0.64	Stabilizing	0.993	D	0.73	prob.delet.	None	None	None	None	N
E/Y	0.5464	ambiguous	0.4638	ambiguous	0.681	Stabilizing	0.993	D	0.733	prob.delet.	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.