TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5052	15379;15380;15381	chr2:178734770;178734769;178734768	chr2:179599497;179599496;179599495
N2AB	4735	14428;14429;14430	chr2:178734770;178734769;178734768	chr2:179599497;179599496;179599495
N2A	3808	11647;11648;11649	chr2:178734770;178734769;178734768	chr2:179599497;179599496;179599495
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAC
• RefSeq wild type template codon: ATG
• Domain: Ig-33
• Domain position: 72
• Structural Position: 154
• Q(SASA): 0.1737
• 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
Y/C	rs950432591	None	1.0	D	0.838	0.908	0.851131110001	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
Y/C	rs950432591	None	1.0	D	0.838	0.908	0.851131110001	gnomAD-4.0.0	6.57022E-06	None	None	None	None	N	None	2.41185E-05	0	None	0	0	None	0	0	0	0	0
Y/F	rs950432591	None	0.999	D	0.702	0.743	0.61690119055	gnomAD-4.0.0	1.36864E-06	None	None	None	None	N	None	0	0	None	7.65697E-05	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
Y/A	0.9918	likely_pathogenic	0.9898	pathogenic	-2.612	Highly Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	N
Y/C	0.8822	likely_pathogenic	0.8531	pathogenic	-2.41	Highly Destabilizing	1.0	D	0.838	deleterious	D	0.826171236	None	None	N
Y/D	0.9974	likely_pathogenic	0.9974	pathogenic	-2.622	Highly Destabilizing	1.0	D	0.879	deleterious	D	0.826171236	None	None	N
Y/E	0.9989	likely_pathogenic	0.9988	pathogenic	-2.4	Highly Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	N
Y/F	0.1379	likely_benign	0.1207	benign	-1.115	Destabilizing	0.999	D	0.702	prob.neutral	D	0.609556009	None	None	N
Y/G	0.9926	likely_pathogenic	0.9912	pathogenic	-3.048	Highly Destabilizing	1.0	D	0.883	deleterious	None	None	None	None	N
Y/H	0.9664	likely_pathogenic	0.9642	pathogenic	-2.069	Highly Destabilizing	1.0	D	0.806	deleterious	D	0.793210419	None	None	N
Y/I	0.7739	likely_pathogenic	0.7079	pathogenic	-1.182	Destabilizing	1.0	D	0.838	deleterious	None	None	None	None	N
Y/K	0.9987	likely_pathogenic	0.9985	pathogenic	-2.018	Highly Destabilizing	1.0	D	0.872	deleterious	None	None	None	None	N
Y/L	0.7822	likely_pathogenic	0.7292	pathogenic	-1.182	Destabilizing	0.999	D	0.768	deleterious	None	None	None	None	N
Y/M	0.9569	likely_pathogenic	0.9417	pathogenic	-1.455	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	N
Y/N	0.9854	likely_pathogenic	0.9832	pathogenic	-2.764	Highly Destabilizing	1.0	D	0.859	deleterious	D	0.826171236	None	None	N
Y/P	0.9978	likely_pathogenic	0.998	pathogenic	-1.672	Destabilizing	1.0	D	0.901	deleterious	None	None	None	None	N
Y/Q	0.9981	likely_pathogenic	0.9978	pathogenic	-2.434	Highly Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	N
Y/R	0.9941	likely_pathogenic	0.9934	pathogenic	-1.977	Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
Y/S	0.9819	likely_pathogenic	0.9791	pathogenic	-3.28	Highly Destabilizing	1.0	D	0.873	deleterious	D	0.826171236	None	None	N
Y/T	0.9903	likely_pathogenic	0.9878	pathogenic	-2.919	Highly Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	N
Y/V	0.741	likely_pathogenic	0.6862	pathogenic	-1.672	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
Y/W	0.718	likely_pathogenic	0.6994	pathogenic	-0.46	Destabilizing	1.0	D	0.792	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.