TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3939	12040;12041;12042	chr2:178741418;178741417;178741416	chr2:179606145;179606144;179606143
N2AB	3622	11089;11090;11091	chr2:178741418;178741417;178741416	chr2:179606145;179606144;179606143
N2A	None	None	chr2:None	chr2:None
N2B	3576	10951;10952;10953	chr2:178741418;178741417;178741416	chr2:179606145;179606144;179606143
Novex-1	3701	11326;11327;11328	chr2:178741418;178741417;178741416	chr2:179606145;179606144;179606143
Novex-2	3768	11527;11528;11529	chr2:178741418;178741417;178741416	chr2:179606145;179606144;179606143
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: H
• RefSeq wild type transcript codon: CAC
• RefSeq wild type template codon: GTG
• Domain: Ig-28
• Domain position: 2
• Structural Position: 2
• Q(SASA): 0.6209
• 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
H/P	None	None	0.013	N	0.309	0.12	None	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
H/Y	None	None	None	N	0.097	0.115	None	gnomAD-4.0.0	1.59108E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.43271E-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
H/A	0.1882	likely_benign	0.1876	benign	-0.218	Destabilizing	None	N	0.272	neutral	None	None	None	None	I
H/C	0.0889	likely_benign	0.094	benign	0.187	Stabilizing	None	N	0.29	neutral	None	None	None	None	I
H/D	0.1879	likely_benign	0.181	benign	-0.487	Destabilizing	0.003	N	0.258	neutral	N	0.430596323	None	None	I
H/E	0.2181	likely_benign	0.2167	benign	-0.412	Destabilizing	0.002	N	0.203	neutral	None	None	None	None	I
H/F	0.1502	likely_benign	0.1638	benign	0.914	Stabilizing	None	N	0.207	neutral	None	None	None	None	I
H/G	0.2497	likely_benign	0.2502	benign	-0.539	Destabilizing	0.001	N	0.31	neutral	None	None	None	None	I
H/I	0.1563	likely_benign	0.1578	benign	0.643	Stabilizing	None	N	0.311	neutral	None	None	None	None	I
H/K	0.1939	likely_benign	0.1931	benign	-0.192	Destabilizing	None	N	0.176	neutral	None	None	None	None	I
H/L	0.0952	likely_benign	0.0936	benign	0.643	Stabilizing	None	N	0.346	neutral	N	0.456861703	None	None	I
H/M	0.3401	ambiguous	0.3457	ambiguous	0.28	Stabilizing	0.021	N	0.45	neutral	None	None	None	None	I
H/N	0.111	likely_benign	0.1068	benign	-0.501	Destabilizing	0.003	N	0.197	neutral	N	0.438083607	None	None	I
H/P	0.4716	ambiguous	0.4219	ambiguous	0.378	Stabilizing	0.013	N	0.309	neutral	N	0.506351438	None	None	I
H/Q	0.1298	likely_benign	0.1339	benign	-0.309	Destabilizing	0.003	N	0.208	neutral	N	0.418841012	None	None	I
H/R	0.0827	likely_benign	0.0832	benign	-0.72	Destabilizing	None	N	0.15	neutral	N	0.381555337	None	None	I
H/S	0.1435	likely_benign	0.1484	benign	-0.415	Destabilizing	None	N	0.169	neutral	None	None	None	None	I
H/T	0.1618	likely_benign	0.1677	benign	-0.229	Destabilizing	None	N	0.211	neutral	None	None	None	None	I
H/V	0.1392	likely_benign	0.1412	benign	0.378	Stabilizing	None	N	0.283	neutral	None	None	None	None	I
H/W	0.2392	likely_benign	0.2504	benign	1.102	Stabilizing	0.132	N	0.42	neutral	None	None	None	None	I
H/Y	0.0485	likely_benign	0.051	benign	1.171	Stabilizing	None	N	0.097	neutral	N	0.35705943	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.