TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32824	98695;98696;98697	chr2:178539595;178539594;178539593	chr2:179404322;179404321;179404320
N2AB	31183	93772;93773;93774	chr2:178539595;178539594;178539593	chr2:179404322;179404321;179404320
N2A	30256	90991;90992;90993	chr2:178539595;178539594;178539593	chr2:179404322;179404321;179404320
N2B	23759	71500;71501;71502	chr2:178539595;178539594;178539593	chr2:179404322;179404321;179404320
Novex-1	23884	71875;71876;71877	chr2:178539595;178539594;178539593	chr2:179404322;179404321;179404320
Novex-2	23951	72076;72077;72078	chr2:178539595;178539594;178539593	chr2:179404322;179404321;179404320
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGT
• RefSeq wild type template codon: CCA
• Domain: Fn3-127
• Domain position: 30
• Structural Position: 31
• Q(SASA): 0.2407
• 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/D	None	None	1.0	N	0.836	0.511	0.443797312901	gnomAD-4.0.0	6.84179E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.15931E-05	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	0.9282	likely_pathogenic	0.9102	pathogenic	-0.287	Destabilizing	1.0	D	0.725	prob.delet.	N	0.514633824	None	None	I
G/C	0.9787	likely_pathogenic	0.973	pathogenic	-0.735	Destabilizing	1.0	D	0.784	deleterious	D	0.542399317	None	None	I
G/D	0.9931	likely_pathogenic	0.9917	pathogenic	-0.674	Destabilizing	1.0	D	0.836	deleterious	N	0.513619866	None	None	I
G/E	0.9957	likely_pathogenic	0.9949	pathogenic	-0.844	Destabilizing	1.0	D	0.844	deleterious	None	None	None	None	I
G/F	0.998	likely_pathogenic	0.9976	pathogenic	-1.116	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	I
G/H	0.9972	likely_pathogenic	0.9966	pathogenic	-0.623	Destabilizing	1.0	D	0.804	deleterious	None	None	None	None	I
G/I	0.998	likely_pathogenic	0.9975	pathogenic	-0.411	Destabilizing	1.0	D	0.784	deleterious	None	None	None	None	I
G/K	0.9975	likely_pathogenic	0.9969	pathogenic	-0.722	Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	I
G/L	0.9967	likely_pathogenic	0.9961	pathogenic	-0.411	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	I
G/M	0.9984	likely_pathogenic	0.998	pathogenic	-0.286	Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	I
G/N	0.9938	likely_pathogenic	0.9922	pathogenic	-0.316	Destabilizing	1.0	D	0.804	deleterious	None	None	None	None	I
G/P	0.9995	likely_pathogenic	0.9993	pathogenic	-0.336	Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	I
G/Q	0.9956	likely_pathogenic	0.9947	pathogenic	-0.647	Destabilizing	1.0	D	0.822	deleterious	None	None	None	None	I
G/R	0.9886	likely_pathogenic	0.986	pathogenic	-0.274	Destabilizing	1.0	D	0.827	deleterious	N	0.49602259	None	None	I
G/S	0.9195	likely_pathogenic	0.8905	pathogenic	-0.449	Destabilizing	1.0	D	0.803	deleterious	N	0.503655912	None	None	I
G/T	0.992	likely_pathogenic	0.9896	pathogenic	-0.555	Destabilizing	1.0	D	0.842	deleterious	None	None	None	None	I
G/V	0.9953	likely_pathogenic	0.9941	pathogenic	-0.336	Destabilizing	1.0	D	0.802	deleterious	N	0.510051921	None	None	I
G/W	0.9952	likely_pathogenic	0.9946	pathogenic	-1.273	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	I
G/Y	0.9972	likely_pathogenic	0.9966	pathogenic	-0.903	Destabilizing	1.0	D	0.773	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.