TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19663	59212;59213;59214	chr2:178593221;178593220;178593219	chr2:179457948;179457947;179457946
N2AB	18022	54289;54290;54291	chr2:178593221;178593220;178593219	chr2:179457948;179457947;179457946
N2A	17095	51508;51509;51510	chr2:178593221;178593220;178593219	chr2:179457948;179457947;179457946
N2B	10598	32017;32018;32019	chr2:178593221;178593220;178593219	chr2:179457948;179457947;179457946
Novex-1	10723	32392;32393;32394	chr2:178593221;178593220;178593219	chr2:179457948;179457947;179457946
Novex-2	10790	32593;32594;32595	chr2:178593221;178593220;178593219	chr2:179457948;179457947;179457946
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGA
• RefSeq wild type template codon: CCT
• Domain: Fn3-30
• Domain position: 85
• Structural Position: 118
• Q(SASA): 0.1717
• 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
G/E	None	None	1.0	D	0.939	0.592	0.610882576163	gnomAD-4.0.0	1.20034E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.31252E-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
G/A	0.6149	likely_pathogenic	0.604	pathogenic	-0.819	Destabilizing	1.0	D	0.691	prob.neutral	D	0.548310434	None	None	N
G/C	0.8794	likely_pathogenic	0.8659	pathogenic	-1.038	Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	N
G/D	0.9834	likely_pathogenic	0.9817	pathogenic	-1.422	Destabilizing	1.0	D	0.887	deleterious	None	None	None	None	N
G/E	0.9891	likely_pathogenic	0.9888	pathogenic	-1.518	Destabilizing	1.0	D	0.939	deleterious	D	0.55941325	None	None	N
G/F	0.9966	likely_pathogenic	0.9966	pathogenic	-1.26	Destabilizing	1.0	D	0.907	deleterious	None	None	None	None	N
G/H	0.9906	likely_pathogenic	0.9893	pathogenic	-1.254	Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	N
G/I	0.9906	likely_pathogenic	0.9903	pathogenic	-0.603	Destabilizing	1.0	D	0.915	deleterious	None	None	None	None	N
G/K	0.9954	likely_pathogenic	0.9952	pathogenic	-1.275	Destabilizing	1.0	D	0.937	deleterious	None	None	None	None	N
G/L	0.9881	likely_pathogenic	0.9871	pathogenic	-0.603	Destabilizing	1.0	D	0.922	deleterious	None	None	None	None	N
G/M	0.9907	likely_pathogenic	0.9902	pathogenic	-0.48	Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	N
G/N	0.9778	likely_pathogenic	0.9753	pathogenic	-0.946	Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	N
G/P	0.9986	likely_pathogenic	0.9985	pathogenic	-0.637	Destabilizing	1.0	D	0.934	deleterious	None	None	None	None	N
G/Q	0.9878	likely_pathogenic	0.9875	pathogenic	-1.229	Destabilizing	1.0	D	0.925	deleterious	None	None	None	None	N
G/R	0.9856	likely_pathogenic	0.9851	pathogenic	-0.853	Destabilizing	1.0	D	0.941	deleterious	D	0.541055505	None	None	N
G/S	0.225	likely_benign	0.2063	benign	-1.141	Destabilizing	1.0	D	0.818	deleterious	None	None	None	None	N
G/T	0.8107	likely_pathogenic	0.7925	pathogenic	-1.176	Destabilizing	1.0	D	0.933	deleterious	None	None	None	None	N
G/V	0.9786	likely_pathogenic	0.9775	pathogenic	-0.637	Destabilizing	1.0	D	0.925	deleterious	D	0.548817413	None	None	N
G/W	0.9896	likely_pathogenic	0.9886	pathogenic	-1.507	Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	N
G/Y	0.9947	likely_pathogenic	0.9944	pathogenic	-1.146	Destabilizing	1.0	D	0.899	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.