TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18672	56239;56240;56241	chr2:178600890;178600889;178600888	chr2:179465617;179465616;179465615
N2AB	17031	51316;51317;51318	chr2:178600890;178600889;178600888	chr2:179465617;179465616;179465615
N2A	16104	48535;48536;48537	chr2:178600890;178600889;178600888	chr2:179465617;179465616;179465615
N2B	9607	29044;29045;29046	chr2:178600890;178600889;178600888	chr2:179465617;179465616;179465615
Novex-1	9732	29419;29420;29421	chr2:178600890;178600889;178600888	chr2:179465617;179465616;179465615
Novex-2	9799	29620;29621;29622	chr2:178600890;178600889;178600888	chr2:179465617;179465616;179465615
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCC
• RefSeq wild type template codon: CGG
• Domain: Fn3-23
• Domain position: 94
• Structural Position: 122
• Q(SASA): 0.6045
• 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/S	None	None	None	N	0.153	0.056	0.0551355673512	gnomAD-4.0.0	1.59331E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.43386E-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	0.4688	ambiguous	0.4139	ambiguous	-0.749	Destabilizing	0.685	D	0.409	neutral	None	None	None	None	I
A/D	0.3823	ambiguous	0.2253	benign	0.143	Stabilizing	None	N	0.397	neutral	N	0.392818717	None	None	I
A/E	0.2768	likely_benign	0.2467	benign	0.011	Stabilizing	None	N	0.286	neutral	None	None	None	None	I
A/F	0.3599	ambiguous	0.2727	benign	-0.691	Destabilizing	0.366	N	0.507	neutral	None	None	None	None	I
A/G	0.1573	likely_benign	0.1319	benign	-0.298	Destabilizing	0.012	N	0.365	neutral	N	0.447711995	None	None	I
A/H	0.4827	ambiguous	0.3813	ambiguous	-0.344	Destabilizing	0.685	D	0.403	neutral	None	None	None	None	I
A/I	0.2369	likely_benign	0.1963	benign	-0.203	Destabilizing	0.039	N	0.471	neutral	None	None	None	None	I
A/K	0.472	ambiguous	0.4055	ambiguous	-0.445	Destabilizing	0.039	N	0.419	neutral	None	None	None	None	I
A/L	0.1585	likely_benign	0.1417	benign	-0.203	Destabilizing	0.039	N	0.441	neutral	None	None	None	None	I
A/M	0.2111	likely_benign	0.1988	benign	-0.346	Destabilizing	0.366	N	0.391	neutral	None	None	None	None	I
A/N	0.2262	likely_benign	0.1571	benign	-0.16	Destabilizing	0.039	N	0.427	neutral	None	None	None	None	I
A/P	0.2134	likely_benign	0.1907	benign	-0.173	Destabilizing	0.177	N	0.454	neutral	N	0.405094581	None	None	I
A/Q	0.2961	likely_benign	0.2708	benign	-0.368	Destabilizing	0.125	N	0.45	neutral	None	None	None	None	I
A/R	0.4545	ambiguous	0.3821	ambiguous	-0.129	Destabilizing	0.221	N	0.445	neutral	None	None	None	None	I
A/S	0.0922	likely_benign	0.0788	benign	-0.466	Destabilizing	None	N	0.153	neutral	N	0.409500323	None	None	I
A/T	0.0863	likely_benign	0.0789	benign	-0.504	Destabilizing	0.001	N	0.181	neutral	N	0.395283019	None	None	I
A/V	0.1211	likely_benign	0.1056	benign	-0.173	Destabilizing	0.001	N	0.2	neutral	N	0.426760719	None	None	I
A/W	0.7609	likely_pathogenic	0.6657	pathogenic	-0.846	Destabilizing	0.869	D	0.591	neutral	None	None	None	None	I
A/Y	0.474	ambiguous	0.377	ambiguous	-0.477	Destabilizing	0.366	N	0.467	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.