TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3878	11857;11858;11859	chr2:178741601;178741600;178741599	chr2:179606328;179606327;179606326
N2AB	3561	10906;10907;10908	chr2:178741601;178741600;178741599	chr2:179606328;179606327;179606326
N2A	None	None	chr2:None	chr2:None
N2B	3515	10768;10769;10770	chr2:178741601;178741600;178741599	chr2:179606328;179606327;179606326
Novex-1	3640	11143;11144;11145	chr2:178741601;178741600;178741599	chr2:179606328;179606327;179606326
Novex-2	3707	11344;11345;11346	chr2:178741601;178741600;178741599	chr2:179606328;179606327;179606326
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Ig-27
• Domain position: 59
• Structural Position: 139
• Q(SASA): 0.2035
• 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
I/N	None	None	0.996	N	0.663	0.403	None	gnomAD-4.0.0	6.84195E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	1.7337E-04	0	0	0
I/T	None	None	0.92	N	0.539	0.257	None	gnomAD-4.0.0	1.36839E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79889E-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
I/A	0.8264	likely_pathogenic	0.7429	pathogenic	-2.263	Highly Destabilizing	0.863	D	0.533	neutral	None	None	None	None	N
I/C	0.8959	likely_pathogenic	0.8533	pathogenic	-1.533	Destabilizing	0.999	D	0.565	neutral	None	None	None	None	N
I/D	0.9615	likely_pathogenic	0.9376	pathogenic	-2.007	Highly Destabilizing	0.997	D	0.652	neutral	None	None	None	None	N
I/E	0.8867	likely_pathogenic	0.8356	pathogenic	-1.843	Destabilizing	0.997	D	0.641	neutral	None	None	None	None	N
I/F	0.3983	ambiguous	0.3152	benign	-1.269	Destabilizing	0.035	N	0.479	neutral	N	0.51100084	None	None	N
I/G	0.9519	likely_pathogenic	0.918	pathogenic	-2.752	Highly Destabilizing	0.997	D	0.64	neutral	None	None	None	None	N
I/H	0.7812	likely_pathogenic	0.7222	pathogenic	-2.04	Highly Destabilizing	0.999	D	0.673	neutral	None	None	None	None	N
I/K	0.6843	likely_pathogenic	0.5876	pathogenic	-1.74	Destabilizing	0.991	D	0.649	neutral	None	None	None	None	N
I/L	0.2529	likely_benign	0.2033	benign	-0.892	Destabilizing	0.509	D	0.473	neutral	N	0.496664485	None	None	N
I/M	0.1968	likely_benign	0.1641	benign	-0.811	Destabilizing	0.988	D	0.556	neutral	N	0.511601082	None	None	N
I/N	0.6751	likely_pathogenic	0.5677	pathogenic	-1.864	Destabilizing	0.996	D	0.663	neutral	N	0.513906755	None	None	N
I/P	0.9894	likely_pathogenic	0.9822	pathogenic	-1.325	Destabilizing	0.997	D	0.656	neutral	None	None	None	None	N
I/Q	0.743	likely_pathogenic	0.6737	pathogenic	-1.812	Destabilizing	0.997	D	0.664	neutral	None	None	None	None	N
I/R	0.5733	likely_pathogenic	0.4857	ambiguous	-1.348	Destabilizing	0.997	D	0.661	neutral	None	None	None	None	N
I/S	0.7068	likely_pathogenic	0.6144	pathogenic	-2.605	Highly Destabilizing	0.959	D	0.605	neutral	N	0.511817574	None	None	N
I/T	0.6015	likely_pathogenic	0.4845	ambiguous	-2.306	Highly Destabilizing	0.92	D	0.539	neutral	N	0.464989763	None	None	N
I/V	0.174	likely_benign	0.1396	benign	-1.325	Destabilizing	0.061	N	0.243	neutral	N	0.457223387	None	None	N
I/W	0.9258	likely_pathogenic	0.8956	pathogenic	-1.546	Destabilizing	0.999	D	0.692	prob.neutral	None	None	None	None	N
I/Y	0.7594	likely_pathogenic	0.6986	pathogenic	-1.285	Destabilizing	0.964	D	0.557	neutral	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.