TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33765	101518;101519;101520	chr2:178535322;178535321;178535320	chr2:179400049;179400048;179400047
N2AB	32124	96595;96596;96597	chr2:178535322;178535321;178535320	chr2:179400049;179400048;179400047
N2A	31197	93814;93815;93816	chr2:178535322;178535321;178535320	chr2:179400049;179400048;179400047
N2B	24700	74323;74324;74325	chr2:178535322;178535321;178535320	chr2:179400049;179400048;179400047
Novex-1	24825	74698;74699;74700	chr2:178535322;178535321;178535320	chr2:179400049;179400048;179400047
Novex-2	24892	74899;74900;74901	chr2:178535322;178535321;178535320	chr2:179400049;179400048;179400047
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: Fn3-132
• Domain position: 77
• Structural Position: 111
• Q(SASA): 0.1721
• 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	None	None	0.994	N	0.459	0.295	0.316198179892	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-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	0.6466	likely_pathogenic	0.7468	pathogenic	-0.813	Destabilizing	0.999	D	0.652	neutral	N	0.465720017	None	None	N
E/C	0.9807	likely_pathogenic	0.9912	pathogenic	-0.557	Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
E/D	0.8986	likely_pathogenic	0.9403	pathogenic	-1.473	Destabilizing	0.994	D	0.459	neutral	N	0.492435554	None	None	N
E/F	0.988	likely_pathogenic	0.9947	pathogenic	-1.026	Destabilizing	1.0	D	0.888	deleterious	None	None	None	None	N
E/G	0.778	likely_pathogenic	0.8501	pathogenic	-1.138	Destabilizing	1.0	D	0.751	deleterious	N	0.492435554	None	None	N
E/H	0.9557	likely_pathogenic	0.9808	pathogenic	-1.243	Destabilizing	1.0	D	0.655	neutral	None	None	None	None	N
E/I	0.8775	likely_pathogenic	0.9354	pathogenic	0.064	Stabilizing	1.0	D	0.887	deleterious	None	None	None	None	N
E/K	0.6638	likely_pathogenic	0.7818	pathogenic	-0.681	Destabilizing	1.0	D	0.505	neutral	N	0.520423029	None	None	N
E/L	0.9351	likely_pathogenic	0.9674	pathogenic	0.064	Stabilizing	1.0	D	0.858	deleterious	None	None	None	None	N
E/M	0.8969	likely_pathogenic	0.9433	pathogenic	0.567	Stabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
E/N	0.9324	likely_pathogenic	0.9642	pathogenic	-0.976	Destabilizing	1.0	D	0.676	prob.neutral	None	None	None	None	N
E/P	0.9992	likely_pathogenic	0.9995	pathogenic	-0.208	Destabilizing	0.999	D	0.8	deleterious	None	None	None	None	N
E/Q	0.3924	ambiguous	0.4795	ambiguous	-0.865	Destabilizing	1.0	D	0.601	neutral	N	0.468606853	None	None	N
E/R	0.8117	likely_pathogenic	0.8828	pathogenic	-0.673	Destabilizing	1.0	D	0.678	prob.neutral	None	None	None	None	N
E/S	0.7719	likely_pathogenic	0.8424	pathogenic	-1.385	Destabilizing	0.999	D	0.559	neutral	None	None	None	None	N
E/T	0.8169	likely_pathogenic	0.886	pathogenic	-1.093	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
E/V	0.7001	likely_pathogenic	0.8073	pathogenic	-0.208	Destabilizing	1.0	D	0.815	deleterious	N	0.465273461	None	None	N
E/W	0.9965	likely_pathogenic	0.9986	pathogenic	-1.095	Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	N
E/Y	0.9815	likely_pathogenic	0.9923	pathogenic	-0.81	Destabilizing	1.0	D	0.854	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.