TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5324	16195;16196;16197	chr2:178733323;178733322;178733321	chr2:179598050;179598049;179598048
N2AB	5007	15244;15245;15246	chr2:178733323;178733322;178733321	chr2:179598050;179598049;179598048
N2A	4080	12463;12464;12465	chr2:178733323;178733322;178733321	chr2:179598050;179598049;179598048
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: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Ig-36
• Domain position: 64
• Structural Position: 145
• Q(SASA): 0.596
• 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/A	None	None	0.977	N	0.633	0.351	0.500805711387	gnomAD-4.0.0	4.78955E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	6.29631E-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	0.2321	likely_benign	0.2217	benign	-0.8	Destabilizing	0.977	D	0.633	neutral	N	0.496948433	None	None	I
E/C	0.9335	likely_pathogenic	0.919	pathogenic	-0.421	Destabilizing	1.0	D	0.784	deleterious	None	None	None	None	I
E/D	0.1257	likely_benign	0.1208	benign	-0.844	Destabilizing	0.117	N	0.257	neutral	N	0.486855149	None	None	I
E/F	0.8666	likely_pathogenic	0.8528	pathogenic	-0.255	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	I
E/G	0.2197	likely_benign	0.2076	benign	-1.131	Destabilizing	0.993	D	0.667	neutral	N	0.511706	None	None	I
E/H	0.603	likely_pathogenic	0.5643	pathogenic	-0.369	Destabilizing	1.0	D	0.716	prob.delet.	None	None	None	None	I
E/I	0.6768	likely_pathogenic	0.652	pathogenic	0.091	Stabilizing	0.998	D	0.787	deleterious	None	None	None	None	I
E/K	0.3125	likely_benign	0.2782	benign	-0.518	Destabilizing	0.977	D	0.578	neutral	N	0.506136236	None	None	I
E/L	0.5663	likely_pathogenic	0.543	ambiguous	0.091	Stabilizing	0.998	D	0.771	deleterious	None	None	None	None	I
E/M	0.6385	likely_pathogenic	0.6175	pathogenic	0.437	Stabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	I
E/N	0.3073	likely_benign	0.2906	benign	-0.96	Destabilizing	0.99	D	0.725	prob.delet.	None	None	None	None	I
E/P	0.9467	likely_pathogenic	0.9334	pathogenic	-0.185	Destabilizing	0.998	D	0.731	prob.delet.	None	None	None	None	I
E/Q	0.1916	likely_benign	0.1827	benign	-0.824	Destabilizing	0.997	D	0.673	neutral	N	0.484713419	None	None	I
E/R	0.4501	ambiguous	0.4098	ambiguous	-0.17	Destabilizing	0.998	D	0.729	prob.delet.	None	None	None	None	I
E/S	0.2406	likely_benign	0.2293	benign	-1.224	Destabilizing	0.983	D	0.616	neutral	None	None	None	None	I
E/T	0.3512	ambiguous	0.3287	benign	-0.953	Destabilizing	0.998	D	0.695	prob.neutral	None	None	None	None	I
E/V	0.4224	ambiguous	0.3946	ambiguous	-0.185	Destabilizing	0.997	D	0.746	deleterious	N	0.511816535	None	None	I
E/W	0.9656	likely_pathogenic	0.9589	pathogenic	0.002	Stabilizing	1.0	D	0.789	deleterious	None	None	None	None	I
E/Y	0.7986	likely_pathogenic	0.7739	pathogenic	-0.02	Destabilizing	1.0	D	0.753	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.