TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8903	26932;26933;26934	chr2:178713951;178713950;178713949	chr2:179578678;179578677;179578676
N2AB	8586	25981;25982;25983	chr2:178713951;178713950;178713949	chr2:179578678;179578677;179578676
N2A	7659	23200;23201;23202	chr2:178713951;178713950;178713949	chr2:179578678;179578677;179578676
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: GAG
• RefSeq wild type template codon: CTC
• Domain: Ig-74
• Domain position: 74
• Structural Position: 157
• Q(SASA): 0.2917
• 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/Q	None	None	0.996	N	0.65	0.234	0.277730125212	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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	0.1714	likely_benign	0.1712	benign	-0.895	Destabilizing	0.996	D	0.626	neutral	D	0.532827471	None	None	N
E/C	0.846	likely_pathogenic	0.8536	pathogenic	-0.334	Destabilizing	1.0	D	0.769	deleterious	None	None	None	None	N
E/D	0.2995	likely_benign	0.3145	benign	-1.096	Destabilizing	0.998	D	0.489	neutral	N	0.497253353	None	None	N
E/F	0.7367	likely_pathogenic	0.7366	pathogenic	-0.094	Destabilizing	1.0	D	0.822	deleterious	None	None	None	None	N
E/G	0.3507	ambiguous	0.362	ambiguous	-1.346	Destabilizing	0.999	D	0.791	deleterious	N	0.509116637	None	None	N
E/H	0.4422	ambiguous	0.4274	ambiguous	-0.283	Destabilizing	1.0	D	0.728	prob.delet.	None	None	None	None	N
E/I	0.2433	likely_benign	0.2593	benign	0.377	Stabilizing	1.0	D	0.833	deleterious	None	None	None	None	N
E/K	0.1639	likely_benign	0.1681	benign	-0.512	Destabilizing	0.767	D	0.367	neutral	N	0.467082481	None	None	N
E/L	0.3364	likely_benign	0.3498	ambiguous	0.377	Stabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
E/M	0.3534	ambiguous	0.3687	ambiguous	0.972	Stabilizing	1.0	D	0.819	deleterious	None	None	None	None	N
E/N	0.4149	ambiguous	0.4223	ambiguous	-1.093	Destabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	N
E/P	0.9851	likely_pathogenic	0.9858	pathogenic	-0.027	Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	N
E/Q	0.1173	likely_benign	0.1201	benign	-0.869	Destabilizing	0.996	D	0.65	neutral	N	0.490055341	None	None	N
E/R	0.2521	likely_benign	0.2551	benign	-0.312	Destabilizing	0.998	D	0.723	prob.delet.	None	None	None	None	N
E/S	0.2322	likely_benign	0.2294	benign	-1.62	Destabilizing	0.997	D	0.593	neutral	None	None	None	None	N
E/T	0.2063	likely_benign	0.2134	benign	-1.206	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	N
E/V	0.1529	likely_benign	0.1619	benign	-0.027	Destabilizing	0.999	D	0.813	deleterious	N	0.471720297	None	None	N
E/W	0.898	likely_pathogenic	0.9017	pathogenic	0.181	Stabilizing	1.0	D	0.77	deleterious	None	None	None	None	N
E/Y	0.6508	likely_pathogenic	0.6512	pathogenic	0.234	Stabilizing	1.0	D	0.833	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.