TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	13717	41374;41375;41376	chr2:178636578;178636577;178636576	chr2:179501305;179501304;179501303
N2AB	12076	36451;36452;36453	chr2:178636578;178636577;178636576	chr2:179501305;179501304;179501303
N2A	11149	33670;33671;33672	chr2:178636578;178636577;178636576	chr2:179501305;179501304;179501303
N2B	4652	14179;14180;14181	chr2:178636578;178636577;178636576	chr2:179501305;179501304;179501303
Novex-1	4777	14554;14555;14556	chr2:178636578;178636577;178636576	chr2:179501305;179501304;179501303
Novex-2	4844	14755;14756;14757	chr2:178636578;178636577;178636576	chr2:179501305;179501304;179501303
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Ig-87
• Domain position: 34
• Structural Position: 46
• Q(SASA): 0.2221
• Predicted PPI site: N

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
T/I	rs754753030	0.387	1.0	N	0.772	0.421	None	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.91E-06	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
T/A	0.5672	likely_pathogenic	0.6533	pathogenic	-0.785	Destabilizing	0.999	D	0.585	neutral	N	0.48969392	None	None	N
T/C	0.9065	likely_pathogenic	0.9162	pathogenic	-0.361	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	N
T/D	0.9944	likely_pathogenic	0.9963	pathogenic	-0.824	Destabilizing	1.0	D	0.788	deleterious	None	None	None	None	N
T/E	0.9937	likely_pathogenic	0.996	pathogenic	-0.63	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
T/F	0.9727	likely_pathogenic	0.9859	pathogenic	-0.501	Destabilizing	1.0	D	0.81	deleterious	None	None	None	None	N
T/G	0.9203	likely_pathogenic	0.9309	pathogenic	-1.199	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	N
T/H	0.9787	likely_pathogenic	0.9871	pathogenic	-1.272	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
T/I	0.8906	likely_pathogenic	0.9137	pathogenic	0.296	Stabilizing	1.0	D	0.772	deleterious	N	0.356916233	None	None	N
T/K	0.9934	likely_pathogenic	0.9949	pathogenic	-0.185	Destabilizing	1.0	D	0.789	deleterious	N	0.502157437	None	None	N
T/L	0.7728	likely_pathogenic	0.8306	pathogenic	0.296	Stabilizing	0.999	D	0.719	prob.delet.	None	None	None	None	N
T/M	0.7176	likely_pathogenic	0.7872	pathogenic	0.215	Stabilizing	1.0	D	0.755	deleterious	None	None	None	None	N
T/N	0.9324	likely_pathogenic	0.957	pathogenic	-0.831	Destabilizing	1.0	D	0.757	deleterious	None	None	None	None	N
T/P	0.7868	likely_pathogenic	0.837	pathogenic	-0.032	Destabilizing	1.0	D	0.768	deleterious	N	0.502194723	None	None	N
T/Q	0.9783	likely_pathogenic	0.9857	pathogenic	-0.581	Destabilizing	1.0	D	0.759	deleterious	None	None	None	None	N
T/R	0.9906	likely_pathogenic	0.9931	pathogenic	-0.435	Destabilizing	1.0	D	0.767	deleterious	N	0.506691396	None	None	N
T/S	0.6875	likely_pathogenic	0.7462	pathogenic	-1.094	Destabilizing	0.999	D	0.59	neutral	N	0.509489816	None	None	N
T/V	0.6576	likely_pathogenic	0.7051	pathogenic	-0.032	Destabilizing	0.999	D	0.624	neutral	None	None	None	None	N
T/W	0.9959	likely_pathogenic	0.9979	pathogenic	-0.683	Destabilizing	1.0	D	0.778	deleterious	None	None	None	None	N
T/Y	0.987	likely_pathogenic	0.9941	pathogenic	-0.264	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N

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.