TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5874	17845;17846;17847	chr2:178731045;178731044;178731043	chr2:179595772;179595771;179595770
N2AB	5557	16894;16895;16896	chr2:178731045;178731044;178731043	chr2:179595772;179595771;179595770
N2A	4630	14113;14114;14115	chr2:178731045;178731044;178731043	chr2:179595772;179595771;179595770
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: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Ig-42
• Domain position: 52
• Structural Position: 130
• Q(SASA): 0.491
• Predicted PPI site: N

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
T/P	None	None	0.991	N	0.529	0.352	0.561485227407	gnomAD-4.0.0	3.18291E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.71736E-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
T/A	0.1163	likely_benign	0.1345	benign	-0.351	Destabilizing	0.76	D	0.363	neutral	N	0.490519488	None	None	N
T/C	0.5948	likely_pathogenic	0.7118	pathogenic	-0.306	Destabilizing	0.999	D	0.526	neutral	None	None	None	None	N
T/D	0.3948	ambiguous	0.5091	ambiguous	0.558	Stabilizing	0.986	D	0.477	neutral	None	None	None	None	N
T/E	0.3919	ambiguous	0.4758	ambiguous	0.501	Stabilizing	0.986	D	0.485	neutral	None	None	None	None	N
T/F	0.3599	ambiguous	0.4507	ambiguous	-0.825	Destabilizing	0.993	D	0.588	neutral	None	None	None	None	N
T/G	0.269	likely_benign	0.315	benign	-0.491	Destabilizing	0.91	D	0.481	neutral	None	None	None	None	N
T/H	0.3676	ambiguous	0.4392	ambiguous	-0.749	Destabilizing	0.999	D	0.581	neutral	None	None	None	None	N
T/I	0.3509	ambiguous	0.4418	ambiguous	-0.103	Destabilizing	0.991	D	0.534	neutral	N	0.49838961	None	None	N
T/K	0.2706	likely_benign	0.3029	benign	-0.207	Destabilizing	0.986	D	0.478	neutral	None	None	None	None	N
T/L	0.165	likely_benign	0.1919	benign	-0.103	Destabilizing	0.953	D	0.471	neutral	None	None	None	None	N
T/M	0.1126	likely_benign	0.117	benign	-0.058	Destabilizing	0.999	D	0.517	neutral	None	None	None	None	N
T/N	0.1416	likely_benign	0.1751	benign	-0.109	Destabilizing	0.982	D	0.401	neutral	N	0.482553366	None	None	N
T/P	0.421	ambiguous	0.491	ambiguous	-0.157	Destabilizing	0.991	D	0.529	neutral	N	0.508086529	None	None	N
T/Q	0.3025	likely_benign	0.3454	ambiguous	-0.257	Destabilizing	0.993	D	0.516	neutral	None	None	None	None	N
T/R	0.2147	likely_benign	0.2505	benign	-0.024	Destabilizing	0.986	D	0.523	neutral	None	None	None	None	N
T/S	0.1181	likely_benign	0.1409	benign	-0.364	Destabilizing	0.17	N	0.196	neutral	N	0.455444123	None	None	N
T/V	0.2772	likely_benign	0.3301	benign	-0.157	Destabilizing	0.953	D	0.375	neutral	None	None	None	None	N
T/W	0.656	likely_pathogenic	0.7445	pathogenic	-0.841	Destabilizing	0.999	D	0.613	neutral	None	None	None	None	N
T/Y	0.3995	ambiguous	0.511	ambiguous	-0.537	Destabilizing	0.998	D	0.589	neutral	None	None	None	None	N

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.