TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33028	99307;99308;99309	chr2:178538747;178538746;178538745	chr2:179403474;179403473;179403472
N2AB	31387	94384;94385;94386	chr2:178538747;178538746;178538745	chr2:179403474;179403473;179403472
N2A	30460	91603;91604;91605	chr2:178538747;178538746;178538745	chr2:179403474;179403473;179403472
N2B	23963	72112;72113;72114	chr2:178538747;178538746;178538745	chr2:179403474;179403473;179403472
Novex-1	24088	72487;72488;72489	chr2:178538747;178538746;178538745	chr2:179403474;179403473;179403472
Novex-2	24155	72688;72689;72690	chr2:178538747;178538746;178538745	chr2:179403474;179403473;179403472
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Fn3-129
• Domain position: 31
• Structural Position: 33
• Q(SASA): 0.2716
• 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
K/Q	None	None	0.83	N	0.744	0.222	0.240491677333	gnomAD-4.0.0	1.59141E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	0	3.02407E-05

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
K/A	0.6798	likely_pathogenic	0.7569	pathogenic	-0.001	Destabilizing	0.648	D	0.609	neutral	None	None	None	None	I
K/C	0.7496	likely_pathogenic	0.8367	pathogenic	-0.022	Destabilizing	0.993	D	0.843	deleterious	None	None	None	None	I
K/D	0.91	likely_pathogenic	0.9356	pathogenic	-0.007	Destabilizing	0.866	D	0.728	prob.delet.	None	None	None	None	I
K/E	0.4596	ambiguous	0.5033	ambiguous	-0.004	Destabilizing	0.41	N	0.609	neutral	N	0.482558074	None	None	I
K/F	0.9357	likely_pathogenic	0.954	pathogenic	-0.202	Destabilizing	0.98	D	0.824	deleterious	None	None	None	None	I
K/G	0.7025	likely_pathogenic	0.7909	pathogenic	-0.218	Destabilizing	0.866	D	0.742	deleterious	None	None	None	None	I
K/H	0.5094	ambiguous	0.5844	pathogenic	-0.624	Destabilizing	0.98	D	0.733	prob.delet.	None	None	None	None	I
K/I	0.7812	likely_pathogenic	0.8311	pathogenic	0.496	Stabilizing	0.908	D	0.802	deleterious	N	0.487638607	None	None	I
K/L	0.6204	likely_pathogenic	0.691	pathogenic	0.496	Stabilizing	0.866	D	0.742	deleterious	None	None	None	None	I
K/M	0.4996	ambiguous	0.5385	ambiguous	0.427	Stabilizing	0.993	D	0.736	prob.delet.	None	None	None	None	I
K/N	0.7499	likely_pathogenic	0.7974	pathogenic	0.327	Stabilizing	0.83	D	0.739	prob.delet.	N	0.462953593	None	None	I
K/P	0.9824	likely_pathogenic	0.991	pathogenic	0.359	Stabilizing	0.929	D	0.715	prob.delet.	None	None	None	None	I
K/Q	0.2255	likely_benign	0.2737	benign	0.103	Stabilizing	0.83	D	0.744	deleterious	N	0.466551259	None	None	I
K/R	0.0781	likely_benign	0.0949	benign	-0.041	Destabilizing	0.01	N	0.486	neutral	N	0.446925348	None	None	I
K/S	0.7057	likely_pathogenic	0.7676	pathogenic	-0.157	Destabilizing	0.648	D	0.684	prob.neutral	None	None	None	None	I
K/T	0.518	ambiguous	0.5846	pathogenic	-0.006	Destabilizing	0.83	D	0.69	prob.neutral	N	0.432516043	None	None	I
K/V	0.6922	likely_pathogenic	0.746	pathogenic	0.359	Stabilizing	0.866	D	0.783	deleterious	None	None	None	None	I
K/W	0.9036	likely_pathogenic	0.9399	pathogenic	-0.192	Destabilizing	0.993	D	0.844	deleterious	None	None	None	None	I
K/Y	0.8487	likely_pathogenic	0.8796	pathogenic	0.162	Stabilizing	0.929	D	0.808	deleterious	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.