TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19322	58189;58190;58191	chr2:178594530;178594529;178594528	chr2:179459257;179459256;179459255
N2AB	17681	53266;53267;53268	chr2:178594530;178594529;178594528	chr2:179459257;179459256;179459255
N2A	16754	50485;50486;50487	chr2:178594530;178594529;178594528	chr2:179459257;179459256;179459255
N2B	10257	30994;30995;30996	chr2:178594530;178594529;178594528	chr2:179459257;179459256;179459255
Novex-1	10382	31369;31370;31371	chr2:178594530;178594529;178594528	chr2:179459257;179459256;179459255
Novex-2	10449	31570;31571;31572	chr2:178594530;178594529;178594528	chr2:179459257;179459256;179459255
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-28
• Domain position: 39
• Structural Position: 41
• Q(SASA): 0.066
• 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
E/G	rs2050988778	None	1.0	D	0.801	0.548	0.539835882356	gnomAD-4.0.0	1.44039E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.575E-05	0	0
E/Q	None	None	1.0	D	0.755	0.403	0.383760037723	gnomAD-4.0.0	1.59222E-06	None	None	None	None	N	None	0	0	None	0	2.77793E-05	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
E/A	0.9431	likely_pathogenic	0.9053	pathogenic	-1.816	Destabilizing	0.999	D	0.741	deleterious	D	0.527949729	None	None	N
E/C	0.9891	likely_pathogenic	0.9863	pathogenic	-1.103	Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	N
E/D	0.9132	likely_pathogenic	0.8486	pathogenic	-1.87	Destabilizing	0.999	D	0.698	prob.neutral	N	0.506611157	None	None	N
E/F	0.9937	likely_pathogenic	0.9885	pathogenic	-1.486	Destabilizing	1.0	D	0.852	deleterious	None	None	None	None	N
E/G	0.9681	likely_pathogenic	0.9458	pathogenic	-2.204	Highly Destabilizing	1.0	D	0.801	deleterious	D	0.52314079	None	None	N
E/H	0.974	likely_pathogenic	0.9597	pathogenic	-1.417	Destabilizing	1.0	D	0.756	deleterious	None	None	None	None	N
E/I	0.9809	likely_pathogenic	0.9643	pathogenic	-0.703	Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
E/K	0.9702	likely_pathogenic	0.9477	pathogenic	-1.722	Destabilizing	0.999	D	0.686	prob.neutral	N	0.520098916	None	None	N
E/L	0.9836	likely_pathogenic	0.9714	pathogenic	-0.703	Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
E/M	0.9819	likely_pathogenic	0.9672	pathogenic	0.042	Stabilizing	1.0	D	0.81	deleterious	None	None	None	None	N
E/N	0.9853	likely_pathogenic	0.9716	pathogenic	-1.951	Destabilizing	1.0	D	0.78	deleterious	None	None	None	None	N
E/P	0.9998	likely_pathogenic	0.9998	pathogenic	-1.06	Destabilizing	1.0	D	0.812	deleterious	None	None	None	None	N
E/Q	0.7112	likely_pathogenic	0.6122	pathogenic	-1.731	Destabilizing	1.0	D	0.755	deleterious	D	0.523540692	None	None	N
E/R	0.9713	likely_pathogenic	0.9571	pathogenic	-1.455	Destabilizing	1.0	D	0.774	deleterious	None	None	None	None	N
E/S	0.9528	likely_pathogenic	0.9194	pathogenic	-2.6	Highly Destabilizing	0.999	D	0.726	prob.delet.	None	None	None	None	N
E/T	0.9721	likely_pathogenic	0.9537	pathogenic	-2.235	Highly Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
E/V	0.9529	likely_pathogenic	0.9167	pathogenic	-1.06	Destabilizing	1.0	D	0.819	deleterious	N	0.510605942	None	None	N
E/W	0.9959	likely_pathogenic	0.9937	pathogenic	-1.439	Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	N
E/Y	0.9885	likely_pathogenic	0.9799	pathogenic	-1.267	Destabilizing	1.0	D	0.827	deleterious	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.