TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25798	77617;77618;77619	chr2:178568740;178568739;178568738	chr2:179433467;179433466;179433465
N2AB	24157	72694;72695;72696	chr2:178568740;178568739;178568738	chr2:179433467;179433466;179433465
N2A	23230	69913;69914;69915	chr2:178568740;178568739;178568738	chr2:179433467;179433466;179433465
N2B	16733	50422;50423;50424	chr2:178568740;178568739;178568738	chr2:179433467;179433466;179433465
Novex-1	16858	50797;50798;50799	chr2:178568740;178568739;178568738	chr2:179433467;179433466;179433465
Novex-2	16925	50998;50999;51000	chr2:178568740;178568739;178568738	chr2:179433467;179433466;179433465
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Ig-136
• Domain position: 1
• Structural Position: 1
• Q(SASA): 0.1644
• 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/T	rs1246528312	-1.691	0.999	D	0.734	0.584	0.653491938199	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	0	1.67168E-04
P/T	rs1246528312	-1.691	0.999	D	0.734	0.584	0.653491938199	gnomAD-4.0.0	1.59289E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.02608E-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
P/A	0.6127	likely_pathogenic	0.5531	ambiguous	-1.663	Destabilizing	0.767	D	0.363	neutral	D	0.529716107	None	None	N
P/C	0.9771	likely_pathogenic	0.9724	pathogenic	-1.29	Destabilizing	1.0	D	0.804	deleterious	None	None	None	None	N
P/D	0.9978	likely_pathogenic	0.9977	pathogenic	-1.925	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
P/E	0.9956	likely_pathogenic	0.9952	pathogenic	-1.938	Destabilizing	1.0	D	0.77	deleterious	None	None	None	None	N
P/F	0.9986	likely_pathogenic	0.9981	pathogenic	-1.428	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
P/G	0.9567	likely_pathogenic	0.954	pathogenic	-1.957	Destabilizing	0.997	D	0.674	neutral	None	None	None	None	N
P/H	0.9954	likely_pathogenic	0.9946	pathogenic	-1.406	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
P/I	0.9841	likely_pathogenic	0.9761	pathogenic	-0.951	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
P/K	0.997	likely_pathogenic	0.9967	pathogenic	-1.285	Destabilizing	1.0	D	0.78	deleterious	None	None	None	None	N
P/L	0.9312	likely_pathogenic	0.9098	pathogenic	-0.951	Destabilizing	0.999	D	0.749	deleterious	D	0.530476576	None	None	N
P/M	0.9847	likely_pathogenic	0.9802	pathogenic	-0.78	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
P/N	0.9958	likely_pathogenic	0.9951	pathogenic	-1.142	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
P/Q	0.9925	likely_pathogenic	0.9913	pathogenic	-1.398	Destabilizing	1.0	D	0.807	deleterious	D	0.529716107	None	None	N
P/R	0.992	likely_pathogenic	0.9905	pathogenic	-0.713	Destabilizing	0.999	D	0.792	deleterious	D	0.529969597	None	None	N
P/S	0.9598	likely_pathogenic	0.9547	pathogenic	-1.624	Destabilizing	0.998	D	0.715	prob.delet.	D	0.529462618	None	None	N
P/T	0.943	likely_pathogenic	0.93	pathogenic	-1.538	Destabilizing	0.999	D	0.734	prob.delet.	D	0.529969597	None	None	N
P/V	0.9443	likely_pathogenic	0.923	pathogenic	-1.156	Destabilizing	0.999	D	0.707	prob.neutral	None	None	None	None	N
P/W	0.9994	likely_pathogenic	0.9993	pathogenic	-1.568	Destabilizing	1.0	D	0.794	deleterious	None	None	None	None	N
P/Y	0.9984	likely_pathogenic	0.998	pathogenic	-1.285	Destabilizing	1.0	D	0.813	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.