TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9528	28807;28808;28809	chr2:178709737;178709736;178709735	chr2:179574464;179574463;179574462
N2AB	9211	27856;27857;27858	chr2:178709737;178709736;178709735	chr2:179574464;179574463;179574462
N2A	8284	25075;25076;25077	chr2:178709737;178709736;178709735	chr2:179574464;179574463;179574462
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: Y
• RefSeq wild type transcript codon: TAC
• RefSeq wild type template codon: ATG
• Domain: Ig-81
• Domain position: 36
• Structural Position: 49
• Q(SASA): 0.2292
• 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
Y/H	None	None	0.995	None	0.562	0.308	0.360961692134	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
Y/A	0.9437	likely_pathogenic	0.9481	pathogenic	-2.664	Highly Destabilizing	0.919	D	0.597	neutral	None	None	None	None	N
Y/C	0.4683	ambiguous	0.4806	ambiguous	-1.223	Destabilizing	0.999	D	0.695	prob.neutral	None	None	None	None	N
Y/D	0.9167	likely_pathogenic	0.9326	pathogenic	-1.707	Destabilizing	0.984	D	0.716	prob.delet.	None	None	None	None	N
Y/E	0.9422	likely_pathogenic	0.9511	pathogenic	-1.601	Destabilizing	0.988	D	0.665	neutral	None	None	None	None	N
Y/F	0.1177	likely_benign	0.1037	benign	-1.12	Destabilizing	0.896	D	0.472	neutral	None	None	None	None	N
Y/G	0.8965	likely_pathogenic	0.904	pathogenic	-3.001	Highly Destabilizing	0.988	D	0.687	prob.neutral	None	None	None	None	N
Y/H	0.4953	ambiguous	0.5092	ambiguous	-1.346	Destabilizing	0.995	D	0.562	neutral	None	None	None	None	N
Y/I	0.8224	likely_pathogenic	0.8486	pathogenic	-1.611	Destabilizing	0.851	D	0.526	neutral	None	None	None	None	N
Y/K	0.9196	likely_pathogenic	0.9329	pathogenic	-1.336	Destabilizing	0.988	D	0.667	neutral	None	None	None	None	N
Y/L	0.656	likely_pathogenic	0.6749	pathogenic	-1.611	Destabilizing	0.015	N	0.321	neutral	None	None	None	None	N
Y/M	0.8204	likely_pathogenic	0.8301	pathogenic	-1.252	Destabilizing	0.976	D	0.659	neutral	None	None	None	None	N
Y/N	0.6373	likely_pathogenic	0.6741	pathogenic	-1.668	Destabilizing	0.984	D	0.689	prob.neutral	None	None	None	None	N
Y/P	0.9991	likely_pathogenic	0.9991	pathogenic	-1.962	Destabilizing	0.996	D	0.725	prob.delet.	None	None	None	None	N
Y/Q	0.8725	likely_pathogenic	0.8864	pathogenic	-1.646	Destabilizing	0.996	D	0.651	neutral	None	None	None	None	N
Y/R	0.8466	likely_pathogenic	0.8605	pathogenic	-0.82	Destabilizing	0.988	D	0.691	prob.neutral	None	None	None	None	N
Y/S	0.7613	likely_pathogenic	0.7831	pathogenic	-2.215	Highly Destabilizing	0.811	D	0.639	neutral	None	None	None	None	N
Y/T	0.907	likely_pathogenic	0.9205	pathogenic	-2.011	Highly Destabilizing	0.132	N	0.501	neutral	None	None	None	None	N
Y/V	0.7778	likely_pathogenic	0.8047	pathogenic	-1.962	Destabilizing	0.851	D	0.529	neutral	None	None	None	None	N
Y/W	0.646	likely_pathogenic	0.6207	pathogenic	-0.578	Destabilizing	0.999	D	0.56	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.