TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3411	10456;10457;10458	chr2:178759056;178759055;178759054	chr2:179623783;179623782;179623781
N2AB	3411	10456;10457;10458	chr2:178759056;178759055;178759054	chr2:179623783;179623782;179623781
N2A	3411	10456;10457;10458	chr2:178759056;178759055;178759054	chr2:179623783;179623782;179623781
N2B	3365	10318;10319;10320	chr2:178759056;178759055;178759054	chr2:179623783;179623782;179623781
Novex-1	3365	10318;10319;10320	chr2:178759056;178759055;178759054	chr2:179623783;179623782;179623781
Novex-2	3365	10318;10319;10320	chr2:178759056;178759055;178759054	chr2:179623783;179623782;179623781
Novex-3	3411	10456;10457;10458	chr2:178759056;178759055;178759054	chr2:179623783;179623782;179623781

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-24
• Domain position: 67
• Structural Position: 151
• Q(SASA): 0.425
• 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	rs2088211648	None	0.999	D	0.591	0.409	0.579595062312	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
E/K	rs2088211648	None	0.999	D	0.591	0.409	0.579595062312	gnomAD-4.0.0	6.57186E-06	None	None	None	None	N	None	2.41301E-05	0	None	0	0	None	0	0	0	0	0
E/V	rs2088210968	None	1.0	N	0.822	0.585	0.698178878506	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	6.55E-05	0	0	0	None	0	0	0	0	0
E/V	rs2088210968	None	1.0	N	0.822	0.585	0.698178878506	gnomAD-4.0.0	6.57117E-06	None	None	None	None	N	None	0	6.54879E-05	None	0	0	None	0	0	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
E/A	0.1549	likely_benign	0.1303	benign	-0.787	Destabilizing	0.999	D	0.721	prob.delet.	N	0.4825785	None	None	N
E/C	0.929	likely_pathogenic	0.9129	pathogenic	-0.288	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
E/D	0.5007	ambiguous	0.6236	pathogenic	-0.846	Destabilizing	0.999	D	0.483	neutral	N	0.51120803	None	None	N
E/F	0.9308	likely_pathogenic	0.9337	pathogenic	-0.326	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
E/G	0.2689	likely_benign	0.2818	benign	-1.119	Destabilizing	1.0	D	0.775	deleterious	N	0.515983164	None	None	N
E/H	0.7572	likely_pathogenic	0.7766	pathogenic	-0.519	Destabilizing	1.0	D	0.674	neutral	None	None	None	None	N
E/I	0.5676	likely_pathogenic	0.5736	pathogenic	0.106	Stabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
E/K	0.1674	likely_benign	0.1624	benign	-0.286	Destabilizing	0.999	D	0.591	neutral	D	0.592522849	None	None	N
E/L	0.6621	likely_pathogenic	0.6576	pathogenic	0.106	Stabilizing	1.0	D	0.816	deleterious	None	None	None	None	N
E/M	0.6016	likely_pathogenic	0.5643	pathogenic	0.514	Stabilizing	1.0	D	0.792	deleterious	None	None	None	None	N
E/N	0.5593	ambiguous	0.6437	pathogenic	-0.78	Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	N
E/P	0.979	likely_pathogenic	0.9834	pathogenic	-0.17	Destabilizing	1.0	D	0.83	deleterious	None	None	None	None	N
E/Q	0.1701	likely_benign	0.1467	benign	-0.658	Destabilizing	1.0	D	0.635	neutral	N	0.514732231	None	None	N
E/R	0.2935	likely_benign	0.2703	benign	-0.052	Destabilizing	1.0	D	0.72	prob.delet.	None	None	None	None	N
E/S	0.2942	likely_benign	0.2953	benign	-1.036	Destabilizing	0.999	D	0.642	neutral	None	None	None	None	N
E/T	0.3288	likely_benign	0.3337	benign	-0.757	Destabilizing	1.0	D	0.818	deleterious	None	None	None	None	N
E/V	0.3594	ambiguous	0.3549	ambiguous	-0.17	Destabilizing	1.0	D	0.822	deleterious	N	0.50988391	None	None	N
E/W	0.9796	likely_pathogenic	0.981	pathogenic	-0.07	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
E/Y	0.8892	likely_pathogenic	0.9057	pathogenic	-0.068	Destabilizing	1.0	D	0.809	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.