TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28983	87172;87173;87174	chr2:178558512;178558511;178558510	chr2:179423239;179423238;179423237
N2AB	27342	82249;82250;82251	chr2:178558512;178558511;178558510	chr2:179423239;179423238;179423237
N2A	26415	79468;79469;79470	chr2:178558512;178558511;178558510	chr2:179423239;179423238;179423237
N2B	19918	59977;59978;59979	chr2:178558512;178558511;178558510	chr2:179423239;179423238;179423237
Novex-1	20043	60352;60353;60354	chr2:178558512;178558511;178558510	chr2:179423239;179423238;179423237
Novex-2	20110	60553;60554;60555	chr2:178558512;178558511;178558510	chr2:179423239;179423238;179423237
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-99
• Domain position: 42
• Structural Position: 44
• Q(SASA): 0.2862
• 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
E/Q	None	None	1.0	N	0.621	0.332	0.368743488249	gnomAD-4.0.0	1.32035E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.44375E-05	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	0.224	likely_benign	0.2229	benign	-0.794	Destabilizing	0.999	D	0.643	neutral	N	0.472402582	None	None	N
E/C	0.8864	likely_pathogenic	0.8792	pathogenic	-0.385	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	N
E/D	0.3951	ambiguous	0.4614	ambiguous	-0.919	Destabilizing	0.999	D	0.445	neutral	N	0.474114736	None	None	N
E/F	0.8914	likely_pathogenic	0.9013	pathogenic	0.042	Stabilizing	1.0	D	0.761	deleterious	None	None	None	None	N
E/G	0.279	likely_benign	0.2928	benign	-1.188	Destabilizing	1.0	D	0.683	prob.neutral	N	0.508651384	None	None	N
E/H	0.6949	likely_pathogenic	0.7173	pathogenic	-0.095	Destabilizing	1.0	D	0.677	prob.neutral	None	None	None	None	N
E/I	0.5029	ambiguous	0.4893	ambiguous	0.292	Stabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
E/K	0.2849	likely_benign	0.2745	benign	-0.359	Destabilizing	0.999	D	0.572	neutral	N	0.460684079	None	None	N
E/L	0.4002	ambiguous	0.396	ambiguous	0.292	Stabilizing	1.0	D	0.794	deleterious	None	None	None	None	N
E/M	0.5678	likely_pathogenic	0.5597	ambiguous	0.671	Stabilizing	1.0	D	0.693	prob.neutral	None	None	None	None	N
E/N	0.607	likely_pathogenic	0.6462	pathogenic	-1.017	Destabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	N
E/P	0.4562	ambiguous	0.464	ambiguous	-0.049	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	N
E/Q	0.1519	likely_benign	0.1471	benign	-0.854	Destabilizing	1.0	D	0.621	neutral	N	0.512939696	None	None	N
E/R	0.4001	ambiguous	0.4015	ambiguous	-0.014	Destabilizing	1.0	D	0.728	prob.delet.	None	None	None	None	N
E/S	0.431	ambiguous	0.455	ambiguous	-1.344	Destabilizing	0.999	D	0.611	neutral	None	None	None	None	N
E/T	0.5003	ambiguous	0.5001	ambiguous	-1.002	Destabilizing	1.0	D	0.759	deleterious	None	None	None	None	N
E/V	0.3048	likely_benign	0.2966	benign	-0.049	Destabilizing	1.0	D	0.778	deleterious	N	0.475068995	None	None	N
E/W	0.9529	likely_pathogenic	0.9622	pathogenic	0.392	Stabilizing	1.0	D	0.751	deleterious	None	None	None	None	N
E/Y	0.8396	likely_pathogenic	0.8598	pathogenic	0.344	Stabilizing	1.0	D	0.748	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.