TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8485	25678;25679;25680	chr2:178717281;178717280;178717279	chr2:179582008;179582007;179582006
N2AB	8168	24727;24728;24729	chr2:178717281;178717280;178717279	chr2:179582008;179582007;179582006
N2A	7241	21946;21947;21948	chr2:178717281;178717280;178717279	chr2:179582008;179582007;179582006
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Ig-70
• Domain position: 30
• Structural Position: 44
• Q(SASA): 0.1764
• 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
I/L	None	None	None	N	0.097	0.229	0.344945010812	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
I/V	rs1560628327	None	0.006	N	0.312	0.163	0.47282010386	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
I/V	rs1560628327	None	0.006	N	0.312	0.163	0.47282010386	gnomAD-4.0.0	1.3194E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.5664E-05	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
I/A	0.7847	likely_pathogenic	0.7109	pathogenic	-1.802	Destabilizing	0.333	N	0.427	neutral	None	None	None	None	I
I/C	0.9296	likely_pathogenic	0.8914	pathogenic	-1.124	Destabilizing	0.995	D	0.558	neutral	None	None	None	None	I
I/D	0.9883	likely_pathogenic	0.9789	pathogenic	-1.248	Destabilizing	0.945	D	0.655	neutral	None	None	None	None	I
I/E	0.9622	likely_pathogenic	0.9372	pathogenic	-1.248	Destabilizing	0.927	D	0.665	neutral	None	None	None	None	I
I/F	0.3487	ambiguous	0.2819	benign	-1.346	Destabilizing	0.002	N	0.269	neutral	N	0.50023505	None	None	I
I/G	0.9536	likely_pathogenic	0.9228	pathogenic	-2.134	Highly Destabilizing	0.707	D	0.647	neutral	None	None	None	None	I
I/H	0.9441	likely_pathogenic	0.9043	pathogenic	-1.413	Destabilizing	0.988	D	0.635	neutral	None	None	None	None	I
I/K	0.9016	likely_pathogenic	0.8427	pathogenic	-1.236	Destabilizing	0.199	N	0.65	neutral	None	None	None	None	I
I/L	0.134	likely_benign	0.0999	benign	-0.957	Destabilizing	None	N	0.097	neutral	N	0.446917853	None	None	I
I/M	0.1201	likely_benign	0.1029	benign	-0.712	Destabilizing	0.003	N	0.208	neutral	D	0.52366927	None	None	I
I/N	0.8813	likely_pathogenic	0.8279	pathogenic	-0.996	Destabilizing	0.928	D	0.653	neutral	N	0.513129108	None	None	I
I/P	0.8998	likely_pathogenic	0.8717	pathogenic	-1.208	Destabilizing	0.981	D	0.653	neutral	None	None	None	None	I
I/Q	0.8888	likely_pathogenic	0.8314	pathogenic	-1.189	Destabilizing	0.778	D	0.653	neutral	None	None	None	None	I
I/R	0.8539	likely_pathogenic	0.7719	pathogenic	-0.656	Destabilizing	0.771	D	0.655	neutral	None	None	None	None	I
I/S	0.847	likely_pathogenic	0.7864	pathogenic	-1.625	Destabilizing	0.646	D	0.571	neutral	D	0.52366927	None	None	I
I/T	0.8247	likely_pathogenic	0.7557	pathogenic	-1.507	Destabilizing	0.354	N	0.498	neutral	N	0.486124083	None	None	I
I/V	0.0996	likely_benign	0.0938	benign	-1.208	Destabilizing	0.006	N	0.312	neutral	N	0.508699817	None	None	I
I/W	0.9321	likely_pathogenic	0.8816	pathogenic	-1.405	Destabilizing	0.997	D	0.629	neutral	None	None	None	None	I
I/Y	0.8329	likely_pathogenic	0.7485	pathogenic	-1.194	Destabilizing	0.165	N	0.557	neutral	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.