TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16326	49201;49202;49203	chr2:178614538;178614537;178614536	chr2:179479265;179479264;179479263
N2AB	14685	44278;44279;44280	chr2:178614538;178614537;178614536	chr2:179479265;179479264;179479263
N2A	13758	41497;41498;41499	chr2:178614538;178614537;178614536	chr2:179479265;179479264;179479263
N2B	7261	22006;22007;22008	chr2:178614538;178614537;178614536	chr2:179479265;179479264;179479263
Novex-1	7386	22381;22382;22383	chr2:178614538;178614537;178614536	chr2:179479265;179479264;179479263
Novex-2	7453	22582;22583;22584	chr2:178614538;178614537;178614536	chr2:179479265;179479264;179479263
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Ig-110
• Domain position: 65
• Structural Position: 151
• Q(SASA): 0.3269
• 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
T/A	rs1247538583	-0.814	0.349	N	0.431	0.14	0.156986980423	gnomAD-2.1.1	8.07E-06	None	None	None	None	N	None	0	5.82E-05	None	0	0	None	0	None	0	0	0
T/A	rs1247538583	-0.814	0.349	N	0.431	0.14	0.156986980423	gnomAD-4.0.0	3.18818E-06	None	None	None	None	N	None	0	4.58169E-05	None	0	0	None	0	0	0	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
T/A	0.1408	likely_benign	0.1906	benign	-0.868	Destabilizing	0.349	N	0.431	neutral	N	0.449487789	None	None	N
T/C	0.5957	likely_pathogenic	0.6118	pathogenic	-0.543	Destabilizing	0.996	D	0.652	neutral	None	None	None	None	N
T/D	0.8963	likely_pathogenic	0.919	pathogenic	-0.414	Destabilizing	0.775	D	0.569	neutral	None	None	None	None	N
T/E	0.8562	likely_pathogenic	0.8925	pathogenic	-0.436	Destabilizing	0.775	D	0.572	neutral	None	None	None	None	N
T/F	0.8438	likely_pathogenic	0.8936	pathogenic	-1.139	Destabilizing	0.961	D	0.713	prob.delet.	None	None	None	None	N
T/G	0.265	likely_benign	0.2979	benign	-1.086	Destabilizing	0.633	D	0.615	neutral	None	None	None	None	N
T/H	0.6605	likely_pathogenic	0.7125	pathogenic	-1.425	Destabilizing	0.989	D	0.699	prob.neutral	None	None	None	None	N
T/I	0.8693	likely_pathogenic	0.909	pathogenic	-0.387	Destabilizing	0.949	D	0.625	neutral	D	0.562342277	None	None	N
T/K	0.7308	likely_pathogenic	0.7946	pathogenic	-0.685	Destabilizing	0.633	D	0.567	neutral	None	None	None	None	N
T/L	0.5923	likely_pathogenic	0.6822	pathogenic	-0.387	Destabilizing	0.775	D	0.557	neutral	None	None	None	None	N
T/M	0.2933	likely_benign	0.3862	ambiguous	0.071	Stabilizing	0.996	D	0.666	neutral	None	None	None	None	N
T/N	0.4566	ambiguous	0.5018	ambiguous	-0.625	Destabilizing	0.565	D	0.493	neutral	D	0.529304912	None	None	N
T/P	0.8792	likely_pathogenic	0.9128	pathogenic	-0.517	Destabilizing	0.949	D	0.621	neutral	D	0.604237849	None	None	N
T/Q	0.6352	likely_pathogenic	0.7043	pathogenic	-0.896	Destabilizing	0.923	D	0.668	neutral	None	None	None	None	N
T/R	0.6365	likely_pathogenic	0.7168	pathogenic	-0.383	Destabilizing	0.923	D	0.655	neutral	None	None	None	None	N
T/S	0.1047	likely_benign	0.1279	benign	-0.895	Destabilizing	0.014	N	0.193	neutral	N	0.427949873	None	None	N
T/V	0.6811	likely_pathogenic	0.7417	pathogenic	-0.517	Destabilizing	0.775	D	0.475	neutral	None	None	None	None	N
T/W	0.963	likely_pathogenic	0.9754	pathogenic	-1.043	Destabilizing	0.996	D	0.723	prob.delet.	None	None	None	None	N
T/Y	0.836	likely_pathogenic	0.8769	pathogenic	-0.797	Destabilizing	0.987	D	0.717	prob.delet.	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.