TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18055	54388;54389;54390	chr2:178605014;178605013;178605012	chr2:179469741;179469740;179469739
N2AB	16414	49465;49466;49467	chr2:178605014;178605013;178605012	chr2:179469741;179469740;179469739
N2A	15487	46684;46685;46686	chr2:178605014;178605013;178605012	chr2:179469741;179469740;179469739
N2B	8990	27193;27194;27195	chr2:178605014;178605013;178605012	chr2:179469741;179469740;179469739
Novex-1	9115	27568;27569;27570	chr2:178605014;178605013;178605012	chr2:179469741;179469740;179469739
Novex-2	9182	27769;27770;27771	chr2:178605014;178605013;178605012	chr2:179469741;179469740;179469739
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: F
• RefSeq wild type transcript codon: TTC
• RefSeq wild type template codon: AAG
• Domain: Ig-114
• Domain position: 88
• Structural Position: 168
• Q(SASA): 0.3195
• 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
F/L	rs776312018	-0.936	0.454	N	0.466	0.197	0.406806705197	gnomAD-4.0.0	1.62352E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.4699E-05	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
F/A	0.4277	ambiguous	0.4076	ambiguous	-1.073	Destabilizing	0.525	D	0.414	neutral	None	None	None	None	N
F/C	0.3135	likely_benign	0.2931	benign	-0.3	Destabilizing	0.997	D	0.509	neutral	N	0.511644122	None	None	N
F/D	0.7323	likely_pathogenic	0.7118	pathogenic	0.622	Stabilizing	0.842	D	0.573	neutral	None	None	None	None	N
F/E	0.6843	likely_pathogenic	0.6543	pathogenic	0.604	Stabilizing	0.842	D	0.534	neutral	None	None	None	None	N
F/G	0.673	likely_pathogenic	0.6618	pathogenic	-1.286	Destabilizing	0.842	D	0.518	neutral	None	None	None	None	N
F/H	0.385	ambiguous	0.3759	ambiguous	0.131	Stabilizing	0.949	D	0.561	neutral	None	None	None	None	N
F/I	0.2731	likely_benign	0.2413	benign	-0.52	Destabilizing	0.801	D	0.501	neutral	N	0.44207218	None	None	N
F/K	0.6423	likely_pathogenic	0.6291	pathogenic	-0.153	Destabilizing	0.029	N	0.33	neutral	None	None	None	None	N
F/L	0.8062	likely_pathogenic	0.7956	pathogenic	-0.52	Destabilizing	0.454	N	0.466	neutral	N	0.441725464	None	None	N
F/M	0.4905	ambiguous	0.453	ambiguous	-0.376	Destabilizing	0.991	D	0.51	neutral	None	None	None	None	N
F/N	0.4883	ambiguous	0.4453	ambiguous	-0.071	Destabilizing	0.842	D	0.577	neutral	None	None	None	None	N
F/P	0.9663	likely_pathogenic	0.9688	pathogenic	-0.685	Destabilizing	0.974	D	0.573	neutral	None	None	None	None	N
F/Q	0.5219	ambiguous	0.4987	ambiguous	-0.155	Destabilizing	0.949	D	0.572	neutral	None	None	None	None	N
F/R	0.5684	likely_pathogenic	0.5737	pathogenic	0.355	Stabilizing	0.728	D	0.569	neutral	None	None	None	None	N
F/S	0.2381	likely_benign	0.22	benign	-0.765	Destabilizing	0.136	N	0.291	neutral	N	0.356413279	None	None	N
F/T	0.3171	likely_benign	0.2895	benign	-0.691	Destabilizing	0.728	D	0.528	neutral	None	None	None	None	N
F/V	0.245	likely_benign	0.2249	benign	-0.685	Destabilizing	0.801	D	0.519	neutral	N	0.426545368	None	None	N
F/W	0.524	ambiguous	0.5324	ambiguous	-0.268	Destabilizing	0.993	D	0.511	neutral	None	None	None	None	N
F/Y	0.1326	likely_benign	0.1312	benign	-0.268	Destabilizing	0.012	N	0.136	neutral	N	0.423659778	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.