TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18690	56293;56294;56295	chr2:178599833;178599832;178599831	chr2:179464560;179464559;179464558
N2AB	17049	51370;51371;51372	chr2:178599833;178599832;178599831	chr2:179464560;179464559;179464558
N2A	16122	48589;48590;48591	chr2:178599833;178599832;178599831	chr2:179464560;179464559;179464558
N2B	9625	29098;29099;29100	chr2:178599833;178599832;178599831	chr2:179464560;179464559;179464558
Novex-1	9750	29473;29474;29475	chr2:178599833;178599832;178599831	chr2:179464560;179464559;179464558
Novex-2	9817	29674;29675;29676	chr2:178599833;178599832;178599831	chr2:179464560;179464559;179464558
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTA
• RefSeq wild type template codon: GAT
• Domain: Ig-116
• Domain position: 3
• Structural Position: 3
• Q(SASA): 0.5409
• 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
L/I	None	None	0.999	N	0.517	0.355	0.490352026379	gnomAD-4.0.0	1.65436E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.94301E-06	0	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
L/A	0.8386	likely_pathogenic	0.8072	pathogenic	-2.382	Highly Destabilizing	0.999	D	0.691	prob.neutral	None	None	None	None	I
L/C	0.8255	likely_pathogenic	0.7823	pathogenic	-1.447	Destabilizing	1.0	D	0.664	neutral	None	None	None	None	I
L/D	0.995	likely_pathogenic	0.9934	pathogenic	-2.434	Highly Destabilizing	1.0	D	0.72	prob.delet.	None	None	None	None	I
L/E	0.9758	likely_pathogenic	0.9704	pathogenic	-2.343	Highly Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	I
L/F	0.6126	likely_pathogenic	0.4931	ambiguous	-1.545	Destabilizing	1.0	D	0.691	prob.neutral	None	None	None	None	I
L/G	0.9558	likely_pathogenic	0.9409	pathogenic	-2.81	Highly Destabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	I
L/H	0.9646	likely_pathogenic	0.9517	pathogenic	-2.184	Highly Destabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	I
L/I	0.1886	likely_benign	0.1721	benign	-1.201	Destabilizing	0.999	D	0.517	neutral	N	0.500944339	None	None	I
L/K	0.9645	likely_pathogenic	0.9592	pathogenic	-1.951	Destabilizing	1.0	D	0.711	prob.delet.	None	None	None	None	I
L/M	0.185	likely_benign	0.1699	benign	-0.881	Destabilizing	1.0	D	0.662	neutral	None	None	None	None	I
L/N	0.974	likely_pathogenic	0.9661	pathogenic	-1.869	Destabilizing	1.0	D	0.723	prob.delet.	None	None	None	None	I
L/P	0.97	likely_pathogenic	0.9556	pathogenic	-1.571	Destabilizing	1.0	D	0.724	prob.delet.	N	0.51516443	None	None	I
L/Q	0.923	likely_pathogenic	0.9018	pathogenic	-1.949	Destabilizing	1.0	D	0.707	prob.neutral	N	0.520647607	None	None	I
L/R	0.951	likely_pathogenic	0.937	pathogenic	-1.384	Destabilizing	1.0	D	0.725	prob.delet.	N	0.494971947	None	None	I
L/S	0.9457	likely_pathogenic	0.9254	pathogenic	-2.466	Highly Destabilizing	1.0	D	0.72	prob.delet.	None	None	None	None	I
L/T	0.7346	likely_pathogenic	0.7042	pathogenic	-2.26	Highly Destabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	I
L/V	0.1958	likely_benign	0.1743	benign	-1.571	Destabilizing	0.999	D	0.565	neutral	N	0.497018599	None	None	I
L/W	0.9276	likely_pathogenic	0.8893	pathogenic	-1.804	Destabilizing	1.0	D	0.706	prob.neutral	None	None	None	None	I
L/Y	0.9505	likely_pathogenic	0.9319	pathogenic	-1.599	Destabilizing	1.0	D	0.716	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.