TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26606	80041;80042;80043	chr2:178566316;178566315;178566314	chr2:179431043;179431042;179431041
N2AB	24965	75118;75119;75120	chr2:178566316;178566315;178566314	chr2:179431043;179431042;179431041
N2A	24038	72337;72338;72339	chr2:178566316;178566315;178566314	chr2:179431043;179431042;179431041
N2B	17541	52846;52847;52848	chr2:178566316;178566315;178566314	chr2:179431043;179431042;179431041
Novex-1	17666	53221;53222;53223	chr2:178566316;178566315;178566314	chr2:179431043;179431042;179431041
Novex-2	17733	53422;53423;53424	chr2:178566316;178566315;178566314	chr2:179431043;179431042;179431041
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCT
• RefSeq wild type template codon: CGA
• Domain: Ig-138
• Domain position: 13
• Structural Position: 23
• Q(SASA): 0.4895
• 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
A/D	rs779734456	-0.37	0.998	N	0.747	0.515	0.42130639912	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.87E-06	0
A/G	rs779734456	None	0.979	N	0.581	0.354	0.311691414656	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	6.17284E-04	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
A/C	0.682	likely_pathogenic	0.7036	pathogenic	-0.715	Destabilizing	1.0	D	0.744	deleterious	None	None	None	None	I
A/D	0.9173	likely_pathogenic	0.9199	pathogenic	-0.88	Destabilizing	0.998	D	0.747	deleterious	N	0.479685399	None	None	I
A/E	0.8461	likely_pathogenic	0.8628	pathogenic	-1.04	Destabilizing	0.995	D	0.731	prob.delet.	None	None	None	None	I
A/F	0.8113	likely_pathogenic	0.7712	pathogenic	-1.127	Destabilizing	0.991	D	0.777	deleterious	None	None	None	None	I
A/G	0.3958	ambiguous	0.4003	ambiguous	-0.573	Destabilizing	0.979	D	0.581	neutral	N	0.519439081	None	None	I
A/H	0.8288	likely_pathogenic	0.821	pathogenic	-0.635	Destabilizing	1.0	D	0.757	deleterious	None	None	None	None	I
A/I	0.7914	likely_pathogenic	0.775	pathogenic	-0.507	Destabilizing	0.938	D	0.665	neutral	None	None	None	None	I
A/K	0.9065	likely_pathogenic	0.9151	pathogenic	-0.839	Destabilizing	0.995	D	0.73	prob.delet.	None	None	None	None	I
A/L	0.7065	likely_pathogenic	0.6945	pathogenic	-0.507	Destabilizing	0.938	D	0.526	neutral	None	None	None	None	I
A/M	0.6836	likely_pathogenic	0.6835	pathogenic	-0.346	Destabilizing	0.999	D	0.749	deleterious	None	None	None	None	I
A/N	0.7412	likely_pathogenic	0.7424	pathogenic	-0.425	Destabilizing	0.998	D	0.773	deleterious	None	None	None	None	I
A/P	0.9556	likely_pathogenic	0.9427	pathogenic	-0.471	Destabilizing	0.998	D	0.73	prob.delet.	N	0.491673588	None	None	I
A/Q	0.732	likely_pathogenic	0.7666	pathogenic	-0.776	Destabilizing	0.998	D	0.759	deleterious	None	None	None	None	I
A/R	0.8266	likely_pathogenic	0.8321	pathogenic	-0.289	Destabilizing	0.995	D	0.755	deleterious	None	None	None	None	I
A/S	0.1549	likely_benign	0.1634	benign	-0.6	Destabilizing	0.979	D	0.562	neutral	N	0.466251952	None	None	I
A/T	0.4697	ambiguous	0.4843	ambiguous	-0.693	Destabilizing	0.958	D	0.675	neutral	N	0.475873511	None	None	I
A/V	0.481	ambiguous	0.4689	ambiguous	-0.471	Destabilizing	0.142	N	0.381	neutral	N	0.456208639	None	None	I
A/W	0.9617	likely_pathogenic	0.9524	pathogenic	-1.25	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	I
A/Y	0.8576	likely_pathogenic	0.8395	pathogenic	-0.918	Destabilizing	0.995	D	0.784	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.