TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32988	99187;99188;99189	chr2:178538973;178538972;178538971	chr2:179403700;179403699;179403698
N2AB	31347	94264;94265;94266	chr2:178538973;178538972;178538971	chr2:179403700;179403699;179403698
N2A	30420	91483;91484;91485	chr2:178538973;178538972;178538971	chr2:179403700;179403699;179403698
N2B	23923	71992;71993;71994	chr2:178538973;178538972;178538971	chr2:179403700;179403699;179403698
Novex-1	24048	72367;72368;72369	chr2:178538973;178538972;178538971	chr2:179403700;179403699;179403698
Novex-2	24115	72568;72569;72570	chr2:178538973;178538972;178538971	chr2:179403700;179403699;179403698
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: Fn3-128
• Domain position: 93
• Structural Position: 125
• Q(SASA): 0.8046
• 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/D	rs1358375083	None	0.058	N	0.277	0.035	0.107399877778	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
E/D	rs1358375083	None	0.058	N	0.277	0.035	0.107399877778	gnomAD-4.0.0	6.57108E-06	None	None	None	None	I	None	2.41324E-05	0	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	0.2648	likely_benign	0.22	benign	-0.205	Destabilizing	0.952	D	0.721	deleterious	N	0.472455724	None	None	I
E/C	0.9356	likely_pathogenic	0.9028	pathogenic	-0.199	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	I
E/D	0.0899	likely_benign	0.0874	benign	-0.228	Destabilizing	0.058	N	0.277	neutral	N	0.391821426	None	None	I
E/F	0.8753	likely_pathogenic	0.816	pathogenic	-0.138	Destabilizing	1.0	D	0.798	deleterious	None	None	None	None	I
E/G	0.296	likely_benign	0.2388	benign	-0.359	Destabilizing	0.986	D	0.659	prob.neutral	N	0.472399795	None	None	I
E/H	0.7109	likely_pathogenic	0.6221	pathogenic	0.372	Stabilizing	1.0	D	0.756	deleterious	None	None	None	None	I
E/I	0.546	ambiguous	0.4505	ambiguous	0.152	Stabilizing	0.995	D	0.82	deleterious	None	None	None	None	I
E/K	0.2859	likely_benign	0.2035	benign	0.304	Stabilizing	0.952	D	0.646	neutral	N	0.47682418	None	None	I
E/L	0.5279	ambiguous	0.4508	ambiguous	0.152	Stabilizing	0.995	D	0.763	deleterious	None	None	None	None	I
E/M	0.6447	likely_pathogenic	0.5663	pathogenic	0.024	Stabilizing	1.0	D	0.795	deleterious	None	None	None	None	I
E/N	0.3378	likely_benign	0.2741	benign	0.054	Stabilizing	0.979	D	0.768	deleterious	None	None	None	None	I
E/P	0.5696	likely_pathogenic	0.4941	ambiguous	0.052	Stabilizing	0.995	D	0.799	deleterious	None	None	None	None	I
E/Q	0.2514	likely_benign	0.2081	benign	0.076	Stabilizing	0.993	D	0.733	deleterious	N	0.477170897	None	None	I
E/R	0.4924	ambiguous	0.3917	ambiguous	0.587	Stabilizing	0.995	D	0.785	deleterious	None	None	None	None	I
E/S	0.2765	likely_benign	0.2299	benign	-0.125	Destabilizing	0.963	D	0.661	prob.neutral	None	None	None	None	I
E/T	0.3609	ambiguous	0.3018	benign	0.004	Stabilizing	0.995	D	0.765	deleterious	None	None	None	None	I
E/V	0.3576	ambiguous	0.29	benign	0.052	Stabilizing	0.993	D	0.753	deleterious	N	0.502759988	None	None	I
E/W	0.9681	likely_pathogenic	0.9491	pathogenic	-0.033	Destabilizing	1.0	D	0.812	deleterious	None	None	None	None	I
E/Y	0.7878	likely_pathogenic	0.7074	pathogenic	0.094	Stabilizing	1.0	D	0.785	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.