TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25617	77074;77075;77076	chr2:178569283;178569282;178569281	chr2:179434010;179434009;179434008
N2AB	23976	72151;72152;72153	chr2:178569283;178569282;178569281	chr2:179434010;179434009;179434008
N2A	23049	69370;69371;69372	chr2:178569283;178569282;178569281	chr2:179434010;179434009;179434008
N2B	16552	49879;49880;49881	chr2:178569283;178569282;178569281	chr2:179434010;179434009;179434008
Novex-1	16677	50254;50255;50256	chr2:178569283;178569282;178569281	chr2:179434010;179434009;179434008
Novex-2	16744	50455;50456;50457	chr2:178569283;178569282;178569281	chr2:179434010;179434009;179434008
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCA
• RefSeq wild type template codon: AGT
• Domain: Fn3-74
• Domain position: 17
• Structural Position: 19
• Q(SASA): 0.1037
• 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
S/L	None	None	0.999	D	0.648	0.47	0.829797144985	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
S/A	0.094	likely_benign	0.1013	benign	-0.722	Destabilizing	0.64	D	0.433	neutral	N	0.479760392	None	None	N
S/C	0.1051	likely_benign	0.1122	benign	-1.067	Destabilizing	1.0	D	0.753	deleterious	None	None	None	None	N
S/D	0.764	likely_pathogenic	0.8206	pathogenic	-2.115	Highly Destabilizing	0.984	D	0.508	neutral	None	None	None	None	N
S/E	0.769	likely_pathogenic	0.8195	pathogenic	-1.991	Destabilizing	0.988	D	0.511	neutral	None	None	None	None	N
S/F	0.2037	likely_benign	0.2439	benign	-0.775	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
S/G	0.1438	likely_benign	0.1682	benign	-1.018	Destabilizing	0.991	D	0.444	neutral	None	None	None	None	N
S/H	0.3853	ambiguous	0.4276	ambiguous	-1.414	Destabilizing	1.0	D	0.759	deleterious	None	None	None	None	N
S/I	0.3363	likely_benign	0.4097	ambiguous	-0.011	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
S/K	0.8081	likely_pathogenic	0.8573	pathogenic	-0.712	Destabilizing	1.0	D	0.504	neutral	None	None	None	None	N
S/L	0.1673	likely_benign	0.1934	benign	-0.011	Destabilizing	0.999	D	0.648	neutral	D	0.543583038	None	None	N
S/M	0.2111	likely_benign	0.243	benign	-0.083	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	N
S/N	0.2869	likely_benign	0.3323	benign	-1.334	Destabilizing	0.875	D	0.518	neutral	None	None	None	None	N
S/P	0.9937	likely_pathogenic	0.9954	pathogenic	-0.215	Destabilizing	0.997	D	0.746	deleterious	D	0.543583038	None	None	N
S/Q	0.6254	likely_pathogenic	0.6748	pathogenic	-1.317	Destabilizing	0.999	D	0.669	neutral	None	None	None	None	N
S/R	0.733	likely_pathogenic	0.7914	pathogenic	-0.765	Destabilizing	1.0	D	0.769	deleterious	None	None	None	None	N
S/T	0.0904	likely_benign	0.0984	benign	-0.965	Destabilizing	0.003	N	0.35	neutral	N	0.521756754	None	None	N
S/V	0.3018	likely_benign	0.3514	ambiguous	-0.215	Destabilizing	0.999	D	0.71	prob.delet.	None	None	None	None	N
S/W	0.4872	ambiguous	0.5513	ambiguous	-1.03	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
S/Y	0.2269	likely_benign	0.2676	benign	-0.588	Destabilizing	1.0	D	0.799	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.