TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4023	12292;12293;12294	chr2:178741166;178741165;178741164	chr2:179605893;179605892;179605891
N2AB	3706	11341;11342;11343	chr2:178741166;178741165;178741164	chr2:179605893;179605892;179605891
N2A	None	None	chr2:None	chr2:None
N2B	3660	11203;11204;11205	chr2:178741166;178741165;178741164	chr2:179605893;179605892;179605891
Novex-1	3785	11578;11579;11580	chr2:178741166;178741165;178741164	chr2:179605893;179605892;179605891
Novex-2	3852	11779;11780;11781	chr2:178741166;178741165;178741164	chr2:179605893;179605892;179605891
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Ig-28
• Domain position: 86
• Structural Position: 171
• Q(SASA): 0.4726
• 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
A/T	None	None	None	N	0.218	0.056	None	gnomAD-4.0.0	1.59211E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.43275E-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
A/C	0.4467	ambiguous	0.4186	ambiguous	-0.75	Destabilizing	0.356	N	0.527	neutral	None	None	None	None	I
A/D	0.3444	ambiguous	0.3373	benign	-0.869	Destabilizing	0.072	N	0.543	neutral	None	None	None	None	I
A/E	0.2197	likely_benign	0.2146	benign	-0.924	Destabilizing	0.029	N	0.415	neutral	N	0.473135512	None	None	I
A/F	0.3274	likely_benign	0.3203	benign	-0.886	Destabilizing	0.214	N	0.617	neutral	None	None	None	None	I
A/G	0.1871	likely_benign	0.1942	benign	-0.943	Destabilizing	None	N	0.195	neutral	N	0.503816964	None	None	I
A/H	0.4386	ambiguous	0.4356	ambiguous	-1.111	Destabilizing	0.356	N	0.575	neutral	None	None	None	None	I
A/I	0.2489	likely_benign	0.2435	benign	-0.269	Destabilizing	0.013	N	0.448	neutral	None	None	None	None	I
A/K	0.303	likely_benign	0.3005	benign	-1.142	Destabilizing	None	N	0.261	neutral	None	None	None	None	I
A/L	0.2125	likely_benign	0.209	benign	-0.269	Destabilizing	0.016	N	0.382	neutral	None	None	None	None	I
A/M	0.2313	likely_benign	0.2305	benign	-0.267	Destabilizing	0.214	N	0.562	neutral	None	None	None	None	I
A/N	0.2976	likely_benign	0.3024	benign	-0.775	Destabilizing	0.072	N	0.548	neutral	None	None	None	None	I
A/P	0.4007	ambiguous	0.4071	ambiguous	-0.378	Destabilizing	0.106	N	0.553	neutral	N	0.511468128	None	None	I
A/Q	0.2978	likely_benign	0.2942	benign	-0.936	Destabilizing	0.12	N	0.594	neutral	None	None	None	None	I
A/R	0.2502	likely_benign	0.2423	benign	-0.782	Destabilizing	0.038	N	0.546	neutral	None	None	None	None	I
A/S	0.1033	likely_benign	0.1045	benign	-1.086	Destabilizing	None	N	0.163	neutral	N	0.374016683	None	None	I
A/T	0.0832	likely_benign	0.0871	benign	-1.046	Destabilizing	None	N	0.218	neutral	N	0.401670663	None	None	I
A/V	0.1402	likely_benign	0.1382	benign	-0.378	Destabilizing	None	N	0.195	neutral	N	0.499033664	None	None	I
A/W	0.7195	likely_pathogenic	0.6924	pathogenic	-1.205	Destabilizing	0.864	D	0.603	neutral	None	None	None	None	I
A/Y	0.4546	ambiguous	0.4328	ambiguous	-0.809	Destabilizing	0.356	N	0.602	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.