TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29010	87253;87254;87255	chr2:178558431;178558430;178558429	chr2:179423158;179423157;179423156
N2AB	27369	82330;82331;82332	chr2:178558431;178558430;178558429	chr2:179423158;179423157;179423156
N2A	26442	79549;79550;79551	chr2:178558431;178558430;178558429	chr2:179423158;179423157;179423156
N2B	19945	60058;60059;60060	chr2:178558431;178558430;178558429	chr2:179423158;179423157;179423156
Novex-1	20070	60433;60434;60435	chr2:178558431;178558430;178558429	chr2:179423158;179423157;179423156
Novex-2	20137	60634;60635;60636	chr2:178558431;178558430;178558429	chr2:179423158;179423157;179423156
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: Fn3-99
• Domain position: 69
• Structural Position: 103
• Q(SASA): 0.2119
• 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/A	rs1702336560	None	0.958	N	0.583	0.39	0.381746406553	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
E/A	rs1702336560	None	0.958	N	0.583	0.39	0.381746406553	gnomAD-4.0.0	2.56226E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	4.78558E-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
E/A	0.2201	likely_benign	0.1772	benign	-0.338	Destabilizing	0.958	D	0.583	neutral	N	0.46977585	None	None	N
E/C	0.8956	likely_pathogenic	0.8337	pathogenic	0.096	Stabilizing	1.0	D	0.778	deleterious	None	None	None	None	N
E/D	0.2704	likely_benign	0.1607	benign	-0.92	Destabilizing	0.004	N	0.153	neutral	N	0.468116782	None	None	N
E/F	0.8769	likely_pathogenic	0.8017	pathogenic	0.482	Stabilizing	1.0	D	0.798	deleterious	None	None	None	None	N
E/G	0.3694	ambiguous	0.2704	benign	-0.805	Destabilizing	0.987	D	0.651	neutral	N	0.485019722	None	None	N
E/H	0.6571	likely_pathogenic	0.5437	ambiguous	0.298	Stabilizing	1.0	D	0.714	prob.delet.	None	None	None	None	N
E/I	0.4785	ambiguous	0.3965	ambiguous	0.972	Stabilizing	0.995	D	0.819	deleterious	None	None	None	None	N
E/K	0.3164	likely_benign	0.2514	benign	-0.187	Destabilizing	0.977	D	0.479	neutral	N	0.506571084	None	None	N
E/L	0.5406	ambiguous	0.4502	ambiguous	0.972	Stabilizing	0.995	D	0.801	deleterious	None	None	None	None	N
E/M	0.5744	likely_pathogenic	0.5115	ambiguous	1.502	Stabilizing	0.997	D	0.79	deleterious	None	None	None	None	N
E/N	0.4606	ambiguous	0.3238	benign	-0.844	Destabilizing	0.956	D	0.667	neutral	None	None	None	None	N
E/P	0.7261	likely_pathogenic	0.5561	ambiguous	0.557	Stabilizing	0.965	D	0.837	deleterious	None	None	None	None	N
E/Q	0.1864	likely_benign	0.1635	benign	-0.563	Destabilizing	0.995	D	0.633	neutral	N	0.504032211	None	None	N
E/R	0.483	ambiguous	0.3949	ambiguous	-0.05	Destabilizing	0.998	D	0.736	prob.delet.	None	None	None	None	N
E/S	0.2765	likely_benign	0.2095	benign	-1.319	Destabilizing	0.968	D	0.487	neutral	None	None	None	None	N
E/T	0.3073	likely_benign	0.2423	benign	-0.892	Destabilizing	0.997	D	0.747	deleterious	None	None	None	None	N
E/V	0.2852	likely_benign	0.237	benign	0.557	Stabilizing	0.99	D	0.799	deleterious	N	0.508651384	None	None	N
E/W	0.9604	likely_pathogenic	0.9318	pathogenic	0.651	Stabilizing	1.0	D	0.778	deleterious	None	None	None	None	N
E/Y	0.7802	likely_pathogenic	0.6637	pathogenic	0.796	Stabilizing	1.0	D	0.81	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.