TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5434	16525;16526;16527	chr2:178732876;178732875;178732874	chr2:179597603;179597602;179597601
N2AB	5117	15574;15575;15576	chr2:178732876;178732875;178732874	chr2:179597603;179597602;179597601
N2A	4190	12793;12794;12795	chr2:178732876;178732875;178732874	chr2:179597603;179597602;179597601
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: S
• RefSeq wild type transcript codon: TCC
• RefSeq wild type template codon: AGG
• Domain: Ig-37
• Domain position: 78
• Structural Position: 162
• Q(SASA): 0.7375
• 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
S/F	None	None	0.998	N	0.521	0.472	0.818133683601	gnomAD-4.0.0	1.59227E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85969E-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
S/A	0.0629	likely_benign	0.0641	benign	-0.184	Destabilizing	0.248	N	0.287	neutral	N	0.42706823	None	None	I
S/C	0.172	likely_benign	0.1674	benign	-0.403	Destabilizing	1.0	D	0.483	neutral	D	0.533582406	None	None	I
S/D	0.3295	likely_benign	0.3691	ambiguous	-0.093	Destabilizing	0.092	N	0.405	neutral	None	None	None	None	I
S/E	0.4017	ambiguous	0.4516	ambiguous	-0.205	Destabilizing	0.942	D	0.345	neutral	None	None	None	None	I
S/F	0.202	likely_benign	0.2184	benign	-0.934	Destabilizing	0.998	D	0.521	neutral	N	0.512109286	None	None	I
S/G	0.0919	likely_benign	0.0892	benign	-0.218	Destabilizing	0.871	D	0.396	neutral	None	None	None	None	I
S/H	0.3019	likely_benign	0.3208	benign	-0.558	Destabilizing	1.0	D	0.418	neutral	None	None	None	None	I
S/I	0.1401	likely_benign	0.1474	benign	-0.225	Destabilizing	0.996	D	0.511	neutral	None	None	None	None	I
S/K	0.4941	ambiguous	0.5127	ambiguous	-0.434	Destabilizing	0.97	D	0.333	neutral	None	None	None	None	I
S/L	0.095	likely_benign	0.0973	benign	-0.225	Destabilizing	0.97	D	0.377	neutral	None	None	None	None	I
S/M	0.1916	likely_benign	0.1946	benign	-0.157	Destabilizing	1.0	D	0.451	neutral	None	None	None	None	I
S/N	0.1272	likely_benign	0.1306	benign	-0.198	Destabilizing	0.97	D	0.367	neutral	None	None	None	None	I
S/P	0.1483	likely_benign	0.157	benign	-0.188	Destabilizing	0.994	D	0.402	neutral	N	0.467626773	None	None	I
S/Q	0.3948	ambiguous	0.4178	ambiguous	-0.439	Destabilizing	0.996	D	0.352	neutral	None	None	None	None	I
S/R	0.3947	ambiguous	0.4079	ambiguous	-0.173	Destabilizing	0.996	D	0.405	neutral	None	None	None	None	I
S/T	0.077	likely_benign	0.08	benign	-0.307	Destabilizing	0.961	D	0.375	neutral	N	0.502200706	None	None	I
S/V	0.1419	likely_benign	0.1482	benign	-0.188	Destabilizing	0.991	D	0.404	neutral	None	None	None	None	I
S/W	0.3536	ambiguous	0.3791	ambiguous	-1.015	Destabilizing	1.0	D	0.68	prob.neutral	None	None	None	None	I
S/Y	0.1974	likely_benign	0.2113	benign	-0.704	Destabilizing	0.998	D	0.524	neutral	D	0.523212102	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.