TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18907	56944;56945;56946	chr2:178598991;178598990;178598989	chr2:179463718;179463717;179463716
N2AB	17266	52021;52022;52023	chr2:178598991;178598990;178598989	chr2:179463718;179463717;179463716
N2A	16339	49240;49241;49242	chr2:178598991;178598990;178598989	chr2:179463718;179463717;179463716
N2B	9842	29749;29750;29751	chr2:178598991;178598990;178598989	chr2:179463718;179463717;179463716
Novex-1	9967	30124;30125;30126	chr2:178598991;178598990;178598989	chr2:179463718;179463717;179463716
Novex-2	10034	30325;30326;30327	chr2:178598991;178598990;178598989	chr2:179463718;179463717;179463716
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: Fn3-25
• Domain position: 24
• Structural Position: 26
• Q(SASA): 0.4213
• 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	rs1238984956	-1.295	0.999	N	0.578	0.186	0.353336612579	gnomAD-2.1.1	3.19E-05	None	None	None	None	I	None	1.14758E-04	0	None	0	0	None	0	None	0	0	0
E/D	rs1238984956	-1.295	0.999	N	0.578	0.186	0.353336612579	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
E/D	rs1238984956	-1.295	0.999	N	0.578	0.186	0.353336612579	gnomAD-4.0.0	6.57886E-06	None	None	None	None	I	None	2.41418E-05	0	None	0	0	None	0	0	0	0	0
E/G	rs1184443568	None	1.0	N	0.73	0.474	0.388010793773	gnomAD-3.1.2	1.32E-05	None	None	None	None	I	None	0	0	0	0	0	None	0	0	2.94E-05	0	0
E/G	rs1184443568	None	1.0	N	0.73	0.474	0.388010793773	gnomAD-4.0.0	1.79982E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.46029E-05	0	0
E/K	None	None	0.999	N	0.644	0.466	0.330589388543	gnomAD-4.0.0	1.59715E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.86669E-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	0.2513	likely_benign	0.2615	benign	-0.255	Destabilizing	0.999	D	0.715	prob.delet.	N	0.430070383	None	None	I
E/C	0.9307	likely_pathogenic	0.9215	pathogenic	-0.288	Destabilizing	1.0	D	0.78	deleterious	None	None	None	None	I
E/D	0.3866	ambiguous	0.4667	ambiguous	-0.851	Destabilizing	0.999	D	0.578	neutral	N	0.520463101	None	None	I
E/F	0.9212	likely_pathogenic	0.9289	pathogenic	0.371	Stabilizing	1.0	D	0.799	deleterious	None	None	None	None	I
E/G	0.4582	ambiguous	0.4727	ambiguous	-0.591	Destabilizing	1.0	D	0.73	prob.delet.	N	0.471727792	None	None	I
E/H	0.8638	likely_pathogenic	0.8792	pathogenic	0.35	Stabilizing	1.0	D	0.689	prob.neutral	None	None	None	None	I
E/I	0.5337	ambiguous	0.5441	ambiguous	0.64	Stabilizing	1.0	D	0.809	deleterious	None	None	None	None	I
E/K	0.398	ambiguous	0.4086	ambiguous	-0.033	Destabilizing	0.999	D	0.644	neutral	N	0.459990646	None	None	I
E/L	0.6262	likely_pathogenic	0.642	pathogenic	0.64	Stabilizing	1.0	D	0.786	deleterious	None	None	None	None	I
E/M	0.6186	likely_pathogenic	0.6404	pathogenic	0.652	Stabilizing	1.0	D	0.754	deleterious	None	None	None	None	I
E/N	0.6985	likely_pathogenic	0.7379	pathogenic	-0.612	Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	I
E/P	0.4981	ambiguous	0.4928	ambiguous	0.364	Stabilizing	1.0	D	0.782	deleterious	None	None	None	None	I
E/Q	0.3264	likely_benign	0.3334	benign	-0.457	Destabilizing	1.0	D	0.695	prob.neutral	N	0.460684079	None	None	I
E/R	0.5958	likely_pathogenic	0.59	pathogenic	0.298	Stabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	I
E/S	0.5566	ambiguous	0.5731	pathogenic	-0.813	Destabilizing	0.999	D	0.671	neutral	None	None	None	None	I
E/T	0.5218	ambiguous	0.5413	ambiguous	-0.525	Destabilizing	1.0	D	0.768	deleterious	None	None	None	None	I
E/V	0.3333	likely_benign	0.359	ambiguous	0.364	Stabilizing	1.0	D	0.757	deleterious	N	0.477749687	None	None	I
E/W	0.9798	likely_pathogenic	0.9829	pathogenic	0.589	Stabilizing	1.0	D	0.781	deleterious	None	None	None	None	I
E/Y	0.8604	likely_pathogenic	0.8668	pathogenic	0.637	Stabilizing	1.0	D	0.772	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.