TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1768	5527;5528;5529	chr2:178776562;178776561;178776560	chr2:179641289;179641288;179641287
N2AB	1768	5527;5528;5529	chr2:178776562;178776561;178776560	chr2:179641289;179641288;179641287
N2A	1768	5527;5528;5529	chr2:178776562;178776561;178776560	chr2:179641289;179641288;179641287
N2B	1722	5389;5390;5391	chr2:178776562;178776561;178776560	chr2:179641289;179641288;179641287
Novex-1	1722	5389;5390;5391	chr2:178776562;178776561;178776560	chr2:179641289;179641288;179641287
Novex-2	1722	5389;5390;5391	chr2:178776562;178776561;178776560	chr2:179641289;179641288;179641287
Novex-3	1768	5527;5528;5529	chr2:178776562;178776561;178776560	chr2:179641289;179641288;179641287

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Ig-8
• Domain position: 66
• Structural Position: 145
• Q(SASA): 0.3413
• 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
Y/C	rs2092250294	None	1.0	D	0.736	0.578	0.725071404083	gnomAD-4.0.0	1.59333E-06	None	None	None	None	I	None	0	2.28666E-05	None	0	0	None	0	0	0	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
Y/A	0.8895	likely_pathogenic	0.8675	pathogenic	-2.063	Highly Destabilizing	1.0	D	0.681	prob.neutral	None	None	None	None	I
Y/C	0.6381	likely_pathogenic	0.554	ambiguous	-0.876	Destabilizing	1.0	D	0.736	prob.delet.	D	0.547333665	None	None	I
Y/D	0.912	likely_pathogenic	0.8672	pathogenic	-0.358	Destabilizing	1.0	D	0.766	deleterious	N	0.505229309	None	None	I
Y/E	0.9793	likely_pathogenic	0.9676	pathogenic	-0.237	Destabilizing	1.0	D	0.752	deleterious	None	None	None	None	I
Y/F	0.1244	likely_benign	0.1225	benign	-0.661	Destabilizing	0.999	D	0.481	neutral	N	0.485117775	None	None	I
Y/G	0.8632	likely_pathogenic	0.8391	pathogenic	-2.397	Highly Destabilizing	1.0	D	0.745	deleterious	None	None	None	None	I
Y/H	0.7147	likely_pathogenic	0.6352	pathogenic	-0.685	Destabilizing	1.0	D	0.694	prob.neutral	D	0.563051106	None	None	I
Y/I	0.9131	likely_pathogenic	0.8891	pathogenic	-1.047	Destabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	I
Y/K	0.9818	likely_pathogenic	0.9722	pathogenic	-1.001	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	I
Y/L	0.7385	likely_pathogenic	0.7143	pathogenic	-1.047	Destabilizing	0.999	D	0.654	neutral	None	None	None	None	I
Y/M	0.9125	likely_pathogenic	0.8969	pathogenic	-0.812	Destabilizing	1.0	D	0.685	prob.neutral	None	None	None	None	I
Y/N	0.7189	likely_pathogenic	0.645	pathogenic	-1.408	Destabilizing	1.0	D	0.761	deleterious	N	0.459145956	None	None	I
Y/P	0.9592	likely_pathogenic	0.9501	pathogenic	-1.382	Destabilizing	1.0	D	0.769	deleterious	None	None	None	None	I
Y/Q	0.9617	likely_pathogenic	0.9425	pathogenic	-1.245	Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	I
Y/R	0.9401	likely_pathogenic	0.908	pathogenic	-0.677	Destabilizing	1.0	D	0.762	deleterious	None	None	None	None	I
Y/S	0.6224	likely_pathogenic	0.5601	ambiguous	-2.027	Highly Destabilizing	1.0	D	0.759	deleterious	N	0.495736981	None	None	I
Y/T	0.8759	likely_pathogenic	0.8468	pathogenic	-1.808	Destabilizing	1.0	D	0.753	deleterious	None	None	None	None	I
Y/V	0.8079	likely_pathogenic	0.7714	pathogenic	-1.382	Destabilizing	1.0	D	0.701	prob.neutral	None	None	None	None	I
Y/W	0.6145	likely_pathogenic	0.5591	ambiguous	-0.176	Destabilizing	1.0	D	0.68	prob.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.