TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7781	23566;23567;23568	chr2:178720421;178720420;178720419	chr2:179585148;179585147;179585146
N2AB	7464	22615;22616;22617	chr2:178720421;178720420;178720419	chr2:179585148;179585147;179585146
N2A	6537	19834;19835;19836	chr2:178720421;178720420;178720419	chr2:179585148;179585147;179585146
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: G
• RefSeq wild type transcript codon: GGA
• RefSeq wild type template codon: CCT
• Domain: Ig-62
• Domain position: 80
• Structural Position: 164
• Q(SASA): 0.2139
• 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/E	rs868631561	None	0.885	D	0.513	0.766	0.739693031037	gnomAD-4.0.0	6.00161E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	3.03767E-04	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	0.9245	likely_pathogenic	0.907	pathogenic	-0.354	Destabilizing	0.988	D	0.611	neutral	D	0.594567887	None	None	I
G/C	0.989	likely_pathogenic	0.985	pathogenic	-0.905	Destabilizing	1.0	D	0.767	deleterious	None	None	None	None	I
G/D	0.9848	likely_pathogenic	0.9814	pathogenic	-0.722	Destabilizing	0.998	D	0.791	deleterious	None	None	None	None	I
G/E	0.9925	likely_pathogenic	0.9913	pathogenic	-0.898	Destabilizing	0.885	D	0.513	neutral	D	0.551932782	None	None	I
G/F	0.9965	likely_pathogenic	0.9956	pathogenic	-1.157	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	I
G/H	0.9973	likely_pathogenic	0.9966	pathogenic	-0.542	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	I
G/I	0.9968	likely_pathogenic	0.9967	pathogenic	-0.567	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	I
G/K	0.9978	likely_pathogenic	0.9975	pathogenic	-0.792	Destabilizing	0.999	D	0.769	deleterious	None	None	None	None	I
G/L	0.9955	likely_pathogenic	0.9947	pathogenic	-0.567	Destabilizing	1.0	D	0.757	deleterious	None	None	None	None	I
G/M	0.9978	likely_pathogenic	0.9972	pathogenic	-0.5	Destabilizing	1.0	D	0.753	deleterious	None	None	None	None	I
G/N	0.9916	likely_pathogenic	0.989	pathogenic	-0.473	Destabilizing	1.0	D	0.75	deleterious	None	None	None	None	I
G/P	0.9996	likely_pathogenic	0.9995	pathogenic	-0.465	Destabilizing	0.999	D	0.781	deleterious	None	None	None	None	I
G/Q	0.9939	likely_pathogenic	0.9924	pathogenic	-0.804	Destabilizing	0.999	D	0.781	deleterious	None	None	None	None	I
G/R	0.9922	likely_pathogenic	0.9904	pathogenic	-0.302	Destabilizing	0.999	D	0.781	deleterious	D	0.656061159	None	None	I
G/S	0.8888	likely_pathogenic	0.8559	pathogenic	-0.585	Destabilizing	0.997	D	0.756	deleterious	None	None	None	None	I
G/T	0.9851	likely_pathogenic	0.9818	pathogenic	-0.701	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	I
G/V	0.9932	likely_pathogenic	0.9922	pathogenic	-0.465	Destabilizing	1.0	D	0.765	deleterious	D	0.656666572	None	None	I
G/W	0.9945	likely_pathogenic	0.9937	pathogenic	-1.268	Destabilizing	1.0	D	0.759	deleterious	None	None	None	None	I
G/Y	0.9955	likely_pathogenic	0.9946	pathogenic	-0.937	Destabilizing	1.0	D	0.804	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.