TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20178	60757;60758;60759	chr2:178591193;178591192;178591191	chr2:179455920;179455919;179455918
N2AB	18537	55834;55835;55836	chr2:178591193;178591192;178591191	chr2:179455920;179455919;179455918
N2A	17610	53053;53054;53055	chr2:178591193;178591192;178591191	chr2:179455920;179455919;179455918
N2B	11113	33562;33563;33564	chr2:178591193;178591192;178591191	chr2:179455920;179455919;179455918
Novex-1	11238	33937;33938;33939	chr2:178591193;178591192;178591191	chr2:179455920;179455919;179455918
Novex-2	11305	34138;34139;34140	chr2:178591193;178591192;178591191	chr2:179455920;179455919;179455918
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Fn3-34
• Domain position: 8
• Structural Position: 8
• Q(SASA): 0.567
• 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
P/R	None	None	1.0	N	0.787	0.465	0.546824882953	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	6.33473E-05	0	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
P/A	0.3032	likely_benign	0.4084	ambiguous	-0.449	Destabilizing	1.0	D	0.757	deleterious	N	0.49270227	None	None	N
P/C	0.8042	likely_pathogenic	0.8628	pathogenic	-0.662	Destabilizing	1.0	D	0.749	deleterious	None	None	None	None	N
P/D	0.7113	likely_pathogenic	0.7898	pathogenic	-0.091	Destabilizing	1.0	D	0.796	deleterious	None	None	None	None	N
P/E	0.5599	ambiguous	0.6706	pathogenic	-0.195	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
P/F	0.8446	likely_pathogenic	0.9013	pathogenic	-0.607	Destabilizing	1.0	D	0.743	deleterious	None	None	None	None	N
P/G	0.6863	likely_pathogenic	0.7676	pathogenic	-0.588	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
P/H	0.498	ambiguous	0.6283	pathogenic	-0.156	Destabilizing	1.0	D	0.732	prob.delet.	D	0.524911535	None	None	N
P/I	0.6648	likely_pathogenic	0.7662	pathogenic	-0.229	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
P/K	0.5549	ambiguous	0.6722	pathogenic	-0.408	Destabilizing	1.0	D	0.794	deleterious	None	None	None	None	N
P/L	0.3825	ambiguous	0.5197	ambiguous	-0.229	Destabilizing	1.0	D	0.789	deleterious	N	0.511065879	None	None	N
P/M	0.6463	likely_pathogenic	0.7355	pathogenic	-0.364	Destabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	N
P/N	0.6668	likely_pathogenic	0.7455	pathogenic	-0.173	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
P/Q	0.4432	ambiguous	0.5635	ambiguous	-0.384	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	N
P/R	0.4415	ambiguous	0.5915	pathogenic	0.059	Stabilizing	1.0	D	0.787	deleterious	N	0.517656607	None	None	N
P/S	0.4577	ambiguous	0.5909	pathogenic	-0.565	Destabilizing	1.0	D	0.796	deleterious	N	0.499298862	None	None	N
P/T	0.3318	likely_benign	0.4533	ambiguous	-0.564	Destabilizing	1.0	D	0.793	deleterious	N	0.490905071	None	None	N
P/V	0.5208	ambiguous	0.6324	pathogenic	-0.267	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
P/W	0.9229	likely_pathogenic	0.9566	pathogenic	-0.69	Destabilizing	1.0	D	0.742	deleterious	None	None	None	None	N
P/Y	0.8084	likely_pathogenic	0.8752	pathogenic	-0.39	Destabilizing	1.0	D	0.766	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.