TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7274	22045;22046;22047	chr2:178723187;178723186;178723185	chr2:179587914;179587913;179587912
N2AB	6957	21094;21095;21096	chr2:178723187;178723186;178723185	chr2:179587914;179587913;179587912
N2A	6030	18313;18314;18315	chr2:178723187;178723186;178723185	chr2:179587914;179587913;179587912
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: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-57
• Domain position: 45
• Structural Position: 102
• Q(SASA): 0.8122
• 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
E/G	None	None	0.801	N	0.395	0.149	0.280181792013	gnomAD-4.0.0	4.80129E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	3.9375E-06	0	3.66327E-05

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
E/A	0.1315	likely_benign	0.1261	benign	0.013	Stabilizing	0.801	D	0.384	neutral	N	0.50332763	None	None	I
E/C	0.7962	likely_pathogenic	0.7612	pathogenic	-0.296	Destabilizing	0.998	D	0.429	neutral	None	None	None	None	I
E/D	0.102	likely_benign	0.0965	benign	-0.454	Destabilizing	0.454	N	0.375	neutral	N	0.447799634	None	None	I
E/F	0.6797	likely_pathogenic	0.6372	pathogenic	-0.069	Destabilizing	0.974	D	0.389	neutral	None	None	None	None	I
E/G	0.0931	likely_benign	0.088	benign	-0.07	Destabilizing	0.801	D	0.395	neutral	N	0.46828955	None	None	I
E/H	0.3431	ambiguous	0.3132	benign	0.574	Stabilizing	0.037	N	0.23	neutral	None	None	None	None	I
E/I	0.3772	ambiguous	0.3409	ambiguous	0.172	Stabilizing	0.974	D	0.399	neutral	None	None	None	None	I
E/K	0.0919	likely_benign	0.084	benign	0.315	Stabilizing	0.669	D	0.383	neutral	N	0.483491076	None	None	I
E/L	0.34	likely_benign	0.3089	benign	0.172	Stabilizing	0.842	D	0.393	neutral	None	None	None	None	I
E/M	0.4316	ambiguous	0.391	ambiguous	-0.079	Destabilizing	0.998	D	0.389	neutral	None	None	None	None	I
E/N	0.1833	likely_benign	0.1632	benign	0.076	Stabilizing	0.067	N	0.254	neutral	None	None	None	None	I
E/P	0.2111	likely_benign	0.2003	benign	0.135	Stabilizing	0.974	D	0.381	neutral	None	None	None	None	I
E/Q	0.1085	likely_benign	0.1045	benign	0.082	Stabilizing	0.051	N	0.212	neutral	N	0.464521313	None	None	I
E/R	0.1435	likely_benign	0.1356	benign	0.517	Stabilizing	0.728	D	0.37	neutral	None	None	None	None	I
E/S	0.1386	likely_benign	0.1281	benign	-0.037	Destabilizing	0.842	D	0.363	neutral	None	None	None	None	I
E/T	0.2003	likely_benign	0.1827	benign	0.045	Stabilizing	0.842	D	0.417	neutral	None	None	None	None	I
E/V	0.2321	likely_benign	0.2128	benign	0.135	Stabilizing	0.966	D	0.384	neutral	N	0.463062401	None	None	I
E/W	0.7652	likely_pathogenic	0.7255	pathogenic	-0.057	Destabilizing	0.998	D	0.479	neutral	None	None	None	None	I
E/Y	0.519	ambiguous	0.4802	ambiguous	0.136	Stabilizing	0.949	D	0.405	neutral	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.