TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25482	76669;76670;76671	chr2:178569688;178569687;178569686	chr2:179434415;179434414;179434413
N2AB	23841	71746;71747;71748	chr2:178569688;178569687;178569686	chr2:179434415;179434414;179434413
N2A	22914	68965;68966;68967	chr2:178569688;178569687;178569686	chr2:179434415;179434414;179434413
N2B	16417	49474;49475;49476	chr2:178569688;178569687;178569686	chr2:179434415;179434414;179434413
Novex-1	16542	49849;49850;49851	chr2:178569688;178569687;178569686	chr2:179434415;179434414;179434413
Novex-2	16609	50050;50051;50052	chr2:178569688;178569687;178569686	chr2:179434415;179434414;179434413
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: C
• RefSeq wild type transcript codon: TGT
• RefSeq wild type template codon: ACA
• Domain: Fn3-73
• Domain position: 78
• Structural Position: 109
• Q(SASA): 0.1018
• 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
C/Y	None	None	0.792	N	0.741	0.329	0.633141044442	gnomAD-4.0.0	2.0538E-06	None	None	None	None	N	None	0	0	None	0	2.53075E-05	None	0	0	1.79945E-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
C/A	0.4742	ambiguous	0.558	ambiguous	-1.742	Destabilizing	0.543	D	0.733	prob.delet.	None	None	None	None	N
C/D	0.9171	likely_pathogenic	0.9537	pathogenic	-1.892	Destabilizing	0.984	D	0.781	deleterious	None	None	None	None	N
C/E	0.9341	likely_pathogenic	0.9642	pathogenic	-1.679	Destabilizing	0.953	D	0.785	deleterious	None	None	None	None	N
C/F	0.283	likely_benign	0.3091	benign	-1.061	Destabilizing	0.007	N	0.627	neutral	N	0.451485806	None	None	N
C/G	0.3452	ambiguous	0.4352	ambiguous	-2.061	Highly Destabilizing	0.939	D	0.759	deleterious	N	0.470595089	None	None	N
C/H	0.5643	likely_pathogenic	0.6657	pathogenic	-2.301	Highly Destabilizing	0.996	D	0.761	deleterious	None	None	None	None	N
C/I	0.7087	likely_pathogenic	0.757	pathogenic	-0.879	Destabilizing	0.59	D	0.729	prob.delet.	None	None	None	None	N
C/K	0.8457	likely_pathogenic	0.9101	pathogenic	-1.637	Destabilizing	0.953	D	0.777	deleterious	None	None	None	None	N
C/L	0.6251	likely_pathogenic	0.6777	pathogenic	-0.879	Destabilizing	0.009	N	0.469	neutral	None	None	None	None	N
C/M	0.7122	likely_pathogenic	0.7638	pathogenic	-0.276	Destabilizing	0.91	D	0.768	deleterious	None	None	None	None	N
C/N	0.7269	likely_pathogenic	0.8234	pathogenic	-2.098	Highly Destabilizing	0.984	D	0.788	deleterious	None	None	None	None	N
C/P	0.9976	likely_pathogenic	0.9986	pathogenic	-1.146	Destabilizing	0.984	D	0.785	deleterious	None	None	None	None	N
C/Q	0.694	likely_pathogenic	0.7947	pathogenic	-1.663	Destabilizing	0.984	D	0.78	deleterious	None	None	None	None	N
C/R	0.4664	ambiguous	0.5766	pathogenic	-1.923	Destabilizing	0.939	D	0.785	deleterious	N	0.423181696	None	None	N
C/S	0.3044	likely_benign	0.3909	ambiguous	-2.395	Highly Destabilizing	0.815	D	0.751	deleterious	N	0.410196543	None	None	N
C/T	0.5263	ambiguous	0.639	pathogenic	-2.028	Highly Destabilizing	0.742	D	0.75	deleterious	None	None	None	None	N
C/V	0.6195	likely_pathogenic	0.6783	pathogenic	-1.146	Destabilizing	0.59	D	0.736	prob.delet.	None	None	None	None	N
C/W	0.6512	likely_pathogenic	0.7066	pathogenic	-1.535	Destabilizing	0.994	D	0.722	prob.delet.	N	0.515747928	None	None	N
C/Y	0.4161	ambiguous	0.4699	ambiguous	-1.335	Destabilizing	0.792	D	0.741	deleterious	N	0.449445578	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.