TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5153	15682;15683;15684	chr2:178734367;178734366;178734365	chr2:179599094;179599093;179599092
N2AB	4836	14731;14732;14733	chr2:178734367;178734366;178734365	chr2:179599094;179599093;179599092
N2A	3909	11950;11951;11952	chr2:178734367;178734366;178734365	chr2:179599094;179599093;179599092
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Ig-34
• Domain position: 79
• Structural Position: 163
• Q(SASA): 0.8319
• Predicted PPI site: I

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
V/D	None	None	1.0	D	0.741	0.686	0.895487556599	gnomAD-4.0.0	1.37438E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	9.02887E-07	1.16981E-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
V/A	0.172	likely_benign	0.1508	benign	-0.365	Destabilizing	0.999	D	0.589	neutral	N	0.509611535	None	None	I
V/C	0.9068	likely_pathogenic	0.8855	pathogenic	-0.803	Destabilizing	1.0	D	0.697	prob.neutral	None	None	None	None	I
V/D	0.8542	likely_pathogenic	0.8234	pathogenic	-0.484	Destabilizing	1.0	D	0.741	deleterious	D	0.740793439	None	None	I
V/E	0.7528	likely_pathogenic	0.691	pathogenic	-0.607	Destabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	I
V/F	0.313	likely_benign	0.2678	benign	-0.774	Destabilizing	1.0	D	0.72	prob.delet.	N	0.510902964	None	None	I
V/G	0.3723	ambiguous	0.3423	ambiguous	-0.414	Destabilizing	1.0	D	0.717	prob.delet.	D	0.543958538	None	None	I
V/H	0.8977	likely_pathogenic	0.868	pathogenic	-0.005	Destabilizing	1.0	D	0.736	prob.delet.	None	None	None	None	I
V/I	0.1297	likely_benign	0.1395	benign	-0.38	Destabilizing	0.997	D	0.527	neutral	D	0.554005926	None	None	I
V/K	0.8579	likely_pathogenic	0.8155	pathogenic	-0.43	Destabilizing	1.0	D	0.724	prob.delet.	None	None	None	None	I
V/L	0.5273	ambiguous	0.5391	ambiguous	-0.38	Destabilizing	0.997	D	0.609	neutral	N	0.508872947	None	None	I
V/M	0.3578	ambiguous	0.3384	benign	-0.599	Destabilizing	1.0	D	0.748	deleterious	None	None	None	None	I
V/N	0.6909	likely_pathogenic	0.6528	pathogenic	-0.22	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	I
V/P	0.9512	likely_pathogenic	0.9464	pathogenic	-0.348	Destabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	I
V/Q	0.7989	likely_pathogenic	0.7395	pathogenic	-0.454	Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	I
V/R	0.8038	likely_pathogenic	0.74	pathogenic	0.052	Stabilizing	1.0	D	0.746	deleterious	None	None	None	None	I
V/S	0.4315	ambiguous	0.3689	ambiguous	-0.505	Destabilizing	1.0	D	0.723	prob.delet.	None	None	None	None	I
V/T	0.3242	likely_benign	0.2993	benign	-0.542	Destabilizing	0.999	D	0.687	prob.neutral	None	None	None	None	I
V/W	0.9457	likely_pathogenic	0.9321	pathogenic	-0.819	Destabilizing	1.0	D	0.746	deleterious	None	None	None	None	I
V/Y	0.7953	likely_pathogenic	0.7424	pathogenic	-0.553	Destabilizing	1.0	D	0.72	prob.delet.	None	None	None	None	I

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.