TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21487	64684;64685;64686	chr2:178585285;178585284;178585283	chr2:179450012;179450011;179450010
N2AB	19846	59761;59762;59763	chr2:178585285;178585284;178585283	chr2:179450012;179450011;179450010
N2A	18919	56980;56981;56982	chr2:178585285;178585284;178585283	chr2:179450012;179450011;179450010
N2B	12422	37489;37490;37491	chr2:178585285;178585284;178585283	chr2:179450012;179450011;179450010
Novex-1	12547	37864;37865;37866	chr2:178585285;178585284;178585283	chr2:179450012;179450011;179450010
Novex-2	12614	38065;38066;38067	chr2:178585285;178585284;178585283	chr2:179450012;179450011;179450010
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-124
• Domain position: 19
• Structural Position: 31
• Q(SASA): 0.254
• 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/D	rs2048679694	None	0.275	N	0.261	0.085	0.30212335484	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	0	2.07125E-04	0
E/D	rs2048679694	None	0.275	N	0.261	0.085	0.30212335484	gnomAD-4.0.0	2.56766E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.34647E-05	2.84917E-05
E/K	rs1485546407	None	0.992	N	0.525	0.401	0.421427970867	gnomAD-3.1.2	1.32E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	2.94E-05	0	0
E/K	rs1485546407	None	0.992	N	0.525	0.401	0.421427970867	gnomAD-4.0.0	4.96307E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	6.7856E-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	0.3497	ambiguous	0.3367	benign	-0.818	Destabilizing	0.996	D	0.621	neutral	N	0.493329787	None	None	N
E/C	0.9502	likely_pathogenic	0.9506	pathogenic	-0.404	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
E/D	0.2936	likely_benign	0.2757	benign	-0.933	Destabilizing	0.275	N	0.261	neutral	N	0.483401515	None	None	N
E/F	0.9178	likely_pathogenic	0.9103	pathogenic	-0.337	Destabilizing	1.0	D	0.802	deleterious	None	None	None	None	N
E/G	0.5413	ambiguous	0.5058	ambiguous	-1.146	Destabilizing	0.998	D	0.703	prob.neutral	D	0.529084224	None	None	N
E/H	0.7456	likely_pathogenic	0.7228	pathogenic	-0.535	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	N
E/I	0.6074	likely_pathogenic	0.5924	pathogenic	0.066	Stabilizing	1.0	D	0.82	deleterious	None	None	None	None	N
E/K	0.4677	ambiguous	0.4243	ambiguous	-0.539	Destabilizing	0.992	D	0.525	neutral	N	0.514492426	None	None	N
E/L	0.6826	likely_pathogenic	0.6602	pathogenic	0.066	Stabilizing	0.999	D	0.797	deleterious	None	None	None	None	N
E/M	0.7259	likely_pathogenic	0.7072	pathogenic	0.451	Stabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
E/N	0.6015	likely_pathogenic	0.585	pathogenic	-0.936	Destabilizing	0.998	D	0.697	prob.neutral	None	None	None	None	N
E/P	0.8023	likely_pathogenic	0.7988	pathogenic	-0.207	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
E/Q	0.2881	likely_benign	0.2707	benign	-0.828	Destabilizing	0.999	D	0.651	neutral	D	0.533424904	None	None	N
E/R	0.6132	likely_pathogenic	0.5783	pathogenic	-0.236	Destabilizing	0.999	D	0.744	deleterious	None	None	None	None	N
E/S	0.4639	ambiguous	0.4464	ambiguous	-1.207	Destabilizing	0.994	D	0.566	neutral	None	None	None	None	N
E/T	0.4356	ambiguous	0.4236	ambiguous	-0.942	Destabilizing	0.999	D	0.739	prob.delet.	None	None	None	None	N
E/V	0.396	ambiguous	0.3949	ambiguous	-0.207	Destabilizing	1.0	D	0.784	deleterious	N	0.493293788	None	None	N
E/W	0.976	likely_pathogenic	0.9717	pathogenic	-0.092	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
E/Y	0.8795	likely_pathogenic	0.8638	pathogenic	-0.101	Destabilizing	1.0	D	0.802	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.