TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29073	87442;87443;87444	chr2:178558137;178558136;178558135	chr2:179422864;179422863;179422862
N2AB	27432	82519;82520;82521	chr2:178558137;178558136;178558135	chr2:179422864;179422863;179422862
N2A	26505	79738;79739;79740	chr2:178558137;178558136;178558135	chr2:179422864;179422863;179422862
N2B	20008	60247;60248;60249	chr2:178558137;178558136;178558135	chr2:179422864;179422863;179422862
Novex-1	20133	60622;60623;60624	chr2:178558137;178558136;178558135	chr2:179422864;179422863;179422862
Novex-2	20200	60823;60824;60825	chr2:178558137;178558136;178558135	chr2:179422864;179422863;179422862
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Ig-145
• Domain position: 29
• Structural Position: 43
• Q(SASA): 0.6945
• 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
L/I	None	None	0.811	N	0.455	0.052	0.298745278005	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	6.33473E-05	0	None	0	0	None	0	0	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
L/A	0.1272	likely_benign	0.1239	benign	-0.801	Destabilizing	0.851	D	0.509	neutral	None	None	None	None	I
L/C	0.3902	ambiguous	0.3517	ambiguous	-0.614	Destabilizing	0.999	D	0.574	neutral	None	None	None	None	I
L/D	0.5254	ambiguous	0.4808	ambiguous	-0.334	Destabilizing	0.976	D	0.62	neutral	None	None	None	None	I
L/E	0.272	likely_benign	0.2411	benign	-0.417	Destabilizing	0.952	D	0.574	neutral	None	None	None	None	I
L/F	0.1038	likely_benign	0.0992	benign	-0.757	Destabilizing	0.984	D	0.519	neutral	N	0.50023505	None	None	I
L/G	0.3754	ambiguous	0.3483	ambiguous	-0.989	Destabilizing	0.976	D	0.582	neutral	None	None	None	None	I
L/H	0.1668	likely_benign	0.1597	benign	-0.311	Destabilizing	0.996	D	0.616	neutral	N	0.510836045	None	None	I
L/I	0.0785	likely_benign	0.0763	benign	-0.419	Destabilizing	0.811	D	0.455	neutral	N	0.467911987	None	None	I
L/K	0.1792	likely_benign	0.1666	benign	-0.518	Destabilizing	0.851	D	0.598	neutral	None	None	None	None	I
L/M	0.0922	likely_benign	0.0909	benign	-0.418	Destabilizing	0.702	D	0.394	neutral	None	None	None	None	I
L/N	0.2536	likely_benign	0.2467	benign	-0.276	Destabilizing	0.976	D	0.622	neutral	None	None	None	None	I
L/P	0.121	likely_benign	0.1095	benign	-0.513	Destabilizing	0.984	D	0.621	neutral	N	0.452153101	None	None	I
L/Q	0.1106	likely_benign	0.1047	benign	-0.501	Destabilizing	0.261	N	0.507	neutral	None	None	None	None	I
L/R	0.1531	likely_benign	0.137	benign	0.046	Stabilizing	0.059	N	0.455	neutral	N	0.485804315	None	None	I
L/S	0.1486	likely_benign	0.1451	benign	-0.728	Destabilizing	0.976	D	0.578	neutral	None	None	None	None	I
L/T	0.1424	likely_benign	0.1359	benign	-0.703	Destabilizing	0.919	D	0.567	neutral	None	None	None	None	I
L/V	0.0729	likely_benign	0.0699	benign	-0.513	Destabilizing	0.026	N	0.259	neutral	N	0.480686497	None	None	I
L/W	0.221	likely_benign	0.2013	benign	-0.786	Destabilizing	0.999	D	0.681	prob.neutral	None	None	None	None	I
L/Y	0.2368	likely_benign	0.221	benign	-0.542	Destabilizing	0.996	D	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.