TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9280	28063;28064;28065	chr2:178711992;178711991;178711990	chr2:179576719;179576718;179576717
N2AB	8963	27112;27113;27114	chr2:178711992;178711991;178711990	chr2:179576719;179576718;179576717
N2A	8036	24331;24332;24333	chr2:178711992;178711991;178711990	chr2:179576719;179576718;179576717
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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: Ig-78
• Domain position: 76
• Structural Position: 159
• Q(SASA): 0.4956
• 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
E/G	None	None	0.999	N	0.692	0.597	0.57347888143	gnomAD-4.0.0	1.59669E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.87061E-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	0.1786	likely_benign	0.2487	benign	-0.659	Destabilizing	0.989	D	0.623	neutral	D	0.527152292	None	None	I
E/C	0.8798	likely_pathogenic	0.9121	pathogenic	-0.22	Destabilizing	1.0	D	0.808	deleterious	None	None	None	None	I
E/D	0.2454	likely_benign	0.2847	benign	-1.087	Destabilizing	0.998	D	0.548	neutral	D	0.532694185	None	None	I
E/F	0.7571	likely_pathogenic	0.7919	pathogenic	-0.695	Destabilizing	0.999	D	0.799	deleterious	None	None	None	None	I
E/G	0.1943	likely_benign	0.3021	benign	-0.953	Destabilizing	0.999	D	0.692	prob.neutral	N	0.488658979	None	None	I
E/H	0.5093	ambiguous	0.5839	pathogenic	-1.011	Destabilizing	1.0	D	0.705	prob.neutral	None	None	None	None	I
E/I	0.3731	ambiguous	0.4587	ambiguous	0.115	Stabilizing	0.995	D	0.714	prob.delet.	None	None	None	None	I
E/K	0.1296	likely_benign	0.1895	benign	-0.29	Destabilizing	0.998	D	0.675	neutral	N	0.504486076	None	None	I
E/L	0.5001	ambiguous	0.6107	pathogenic	0.115	Stabilizing	0.983	D	0.717	prob.delet.	None	None	None	None	I
E/M	0.4875	ambiguous	0.5722	pathogenic	0.56	Stabilizing	1.0	D	0.787	deleterious	None	None	None	None	I
E/N	0.3334	likely_benign	0.4103	ambiguous	-0.566	Destabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	I
E/P	0.9816	likely_pathogenic	0.9915	pathogenic	-0.122	Destabilizing	1.0	D	0.769	deleterious	None	None	None	None	I
E/Q	0.1226	likely_benign	0.1557	benign	-0.522	Destabilizing	0.999	D	0.683	prob.neutral	N	0.50173656	None	None	I
E/R	0.2341	likely_benign	0.3125	benign	-0.244	Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	I
E/S	0.2108	likely_benign	0.2627	benign	-0.844	Destabilizing	0.996	D	0.71	prob.delet.	None	None	None	None	I
E/T	0.228	likely_benign	0.2828	benign	-0.605	Destabilizing	0.998	D	0.709	prob.delet.	None	None	None	None	I
E/V	0.2144	likely_benign	0.2646	benign	-0.122	Destabilizing	0.733	D	0.487	neutral	N	0.515820578	None	None	I
E/W	0.8991	likely_pathogenic	0.9333	pathogenic	-0.62	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	I
E/Y	0.7019	likely_pathogenic	0.7701	pathogenic	-0.459	Destabilizing	1.0	D	0.799	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.