TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20348	61267;61268;61269	chr2:178590683;178590682;178590681	chr2:179455410;179455409;179455408
N2AB	18707	56344;56345;56346	chr2:178590683;178590682;178590681	chr2:179455410;179455409;179455408
N2A	17780	53563;53564;53565	chr2:178590683;178590682;178590681	chr2:179455410;179455409;179455408
N2B	11283	34072;34073;34074	chr2:178590683;178590682;178590681	chr2:179455410;179455409;179455408
Novex-1	11408	34447;34448;34449	chr2:178590683;178590682;178590681	chr2:179455410;179455409;179455408
Novex-2	11475	34648;34649;34650	chr2:178590683;178590682;178590681	chr2:179455410;179455409;179455408
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: Fn3-35
• Domain position: 78
• Structural Position: 111
• Q(SASA): 0.1987
• 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
E/A	rs754621313	-1.125	0.999	N	0.662	0.405	0.371157983038	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.88E-06	0
E/G	None	None	1.0	N	0.749	0.523	0.467247493403	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	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
E/A	0.4008	ambiguous	0.4254	ambiguous	-1.07	Destabilizing	0.999	D	0.662	neutral	N	0.468024195	None	None	I
E/C	0.9175	likely_pathogenic	0.9366	pathogenic	-0.621	Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	I
E/D	0.645	likely_pathogenic	0.7454	pathogenic	-1.481	Destabilizing	0.999	D	0.464	neutral	N	0.496550157	None	None	I
E/F	0.925	likely_pathogenic	0.9361	pathogenic	-0.721	Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	I
E/G	0.5351	ambiguous	0.5434	ambiguous	-1.474	Destabilizing	1.0	D	0.749	deleterious	N	0.503133523	None	None	I
E/H	0.7933	likely_pathogenic	0.8377	pathogenic	-0.998	Destabilizing	1.0	D	0.682	prob.neutral	None	None	None	None	I
E/I	0.5122	ambiguous	0.5796	pathogenic	0.055	Stabilizing	1.0	D	0.882	deleterious	None	None	None	None	I
E/K	0.2558	likely_benign	0.2986	benign	-0.871	Destabilizing	0.999	D	0.522	neutral	N	0.465581887	None	None	I
E/L	0.6587	likely_pathogenic	0.7245	pathogenic	0.055	Stabilizing	1.0	D	0.845	deleterious	None	None	None	None	I
E/M	0.5997	likely_pathogenic	0.649	pathogenic	0.683	Stabilizing	1.0	D	0.825	deleterious	None	None	None	None	I
E/N	0.7504	likely_pathogenic	0.8168	pathogenic	-1.329	Destabilizing	1.0	D	0.714	prob.delet.	None	None	None	None	I
E/P	0.995	likely_pathogenic	0.9964	pathogenic	-0.299	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	I
E/Q	0.187	likely_benign	0.2162	benign	-1.145	Destabilizing	1.0	D	0.616	neutral	D	0.522865901	None	None	I
E/R	0.4739	ambiguous	0.5229	ambiguous	-0.719	Destabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	I
E/S	0.5488	ambiguous	0.6016	pathogenic	-1.796	Destabilizing	0.999	D	0.565	neutral	None	None	None	None	I
E/T	0.5531	ambiguous	0.6065	pathogenic	-1.433	Destabilizing	1.0	D	0.796	deleterious	None	None	None	None	I
E/V	0.3235	likely_benign	0.3621	ambiguous	-0.299	Destabilizing	1.0	D	0.811	deleterious	N	0.469044485	None	None	I
E/W	0.9726	likely_pathogenic	0.9804	pathogenic	-0.585	Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	I
E/Y	0.8848	likely_pathogenic	0.9064	pathogenic	-0.464	Destabilizing	1.0	D	0.841	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.