TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20851	62776;62777;62778	chr2:178589174;178589173;178589172	chr2:179453901;179453900;179453899
N2AB	19210	57853;57854;57855	chr2:178589174;178589173;178589172	chr2:179453901;179453900;179453899
N2A	18283	55072;55073;55074	chr2:178589174;178589173;178589172	chr2:179453901;179453900;179453899
N2B	11786	35581;35582;35583	chr2:178589174;178589173;178589172	chr2:179453901;179453900;179453899
Novex-1	11911	35956;35957;35958	chr2:178589174;178589173;178589172	chr2:179453901;179453900;179453899
Novex-2	11978	36157;36158;36159	chr2:178589174;178589173;178589172	chr2:179453901;179453900;179453899
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGC
• RefSeq wild type template codon: CCG
• Domain: Ig-122
• Domain position: 83
• Structural Position: 164
• Q(SASA): 0.2453
• 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
G/R	None	None	1.0	D	0.862	0.679	0.814518163516	gnomAD-4.0.0	1.59195E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85914E-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	0.9033	likely_pathogenic	0.874	pathogenic	-0.209	Destabilizing	1.0	D	0.76	deleterious	D	0.605943955	None	None	I
G/C	0.9753	likely_pathogenic	0.9616	pathogenic	-0.787	Destabilizing	1.0	D	0.813	deleterious	D	0.618995178	None	None	I
G/D	0.9888	likely_pathogenic	0.9856	pathogenic	-0.543	Destabilizing	1.0	D	0.853	deleterious	D	0.591842632	None	None	I
G/E	0.9939	likely_pathogenic	0.9916	pathogenic	-0.72	Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	I
G/F	0.9972	likely_pathogenic	0.9959	pathogenic	-1.067	Destabilizing	1.0	D	0.842	deleterious	None	None	None	None	I
G/H	0.9975	likely_pathogenic	0.996	pathogenic	-0.458	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	I
G/I	0.9975	likely_pathogenic	0.9966	pathogenic	-0.446	Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	I
G/K	0.9978	likely_pathogenic	0.997	pathogenic	-0.611	Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	I
G/L	0.9962	likely_pathogenic	0.9944	pathogenic	-0.446	Destabilizing	1.0	D	0.834	deleterious	None	None	None	None	I
G/M	0.9976	likely_pathogenic	0.9969	pathogenic	-0.404	Destabilizing	1.0	D	0.812	deleterious	None	None	None	None	I
G/N	0.9916	likely_pathogenic	0.9876	pathogenic	-0.271	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	I
G/P	0.9997	likely_pathogenic	0.9995	pathogenic	-0.338	Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	I
G/Q	0.9937	likely_pathogenic	0.991	pathogenic	-0.584	Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	I
G/R	0.9924	likely_pathogenic	0.9891	pathogenic	-0.188	Destabilizing	1.0	D	0.862	deleterious	D	0.611253381	None	None	I
G/S	0.8794	likely_pathogenic	0.8238	pathogenic	-0.383	Destabilizing	1.0	D	0.808	deleterious	D	0.581425583	None	None	I
G/T	0.9858	likely_pathogenic	0.9785	pathogenic	-0.498	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	I
G/V	0.9932	likely_pathogenic	0.9903	pathogenic	-0.338	Destabilizing	1.0	D	0.835	deleterious	D	0.627878155	None	None	I
G/W	0.9974	likely_pathogenic	0.9961	pathogenic	-1.194	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	I
G/Y	0.9965	likely_pathogenic	0.9947	pathogenic	-0.843	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.