TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8343	25252;25253;25254	chr2:178717979;178717978;178717977	chr2:179582706;179582705;179582704
N2AB	8026	24301;24302;24303	chr2:178717979;178717978;178717977	chr2:179582706;179582705;179582704
N2A	7099	21520;21521;21522	chr2:178717979;178717978;178717977	chr2:179582706;179582705;179582704
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: GGG
• RefSeq wild type template codon: CCC
• Domain: Ig-68
• Domain position: 80
• Structural Position: 164
• Q(SASA): 0.2637
• 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/A	rs1288642142	-0.155	1.0	D	0.739	0.61	0.63749958327	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	4.65E-05	0	0
G/A	rs1288642142	-0.155	1.0	D	0.739	0.61	0.63749958327	gnomAD-4.0.0	1.59204E-06	None	None	None	None	I	None	0	0	None	0	0	None	1.88246E-05	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
G/A	0.7955	likely_pathogenic	0.8948	pathogenic	-0.479	Destabilizing	1.0	D	0.739	prob.delet.	D	0.62676554	None	None	I
G/C	0.962	likely_pathogenic	0.9859	pathogenic	-0.959	Destabilizing	1.0	D	0.798	deleterious	None	None	None	None	I
G/D	0.9508	likely_pathogenic	0.979	pathogenic	-0.871	Destabilizing	1.0	D	0.846	deleterious	None	None	None	None	I
G/E	0.9706	likely_pathogenic	0.9891	pathogenic	-1.044	Destabilizing	1.0	D	0.825	deleterious	D	0.617044985	None	None	I
G/F	0.9908	likely_pathogenic	0.9959	pathogenic	-1.222	Destabilizing	1.0	D	0.83	deleterious	None	None	None	None	I
G/H	0.9886	likely_pathogenic	0.9963	pathogenic	-0.671	Destabilizing	1.0	D	0.8	deleterious	None	None	None	None	I
G/I	0.9905	likely_pathogenic	0.9968	pathogenic	-0.644	Destabilizing	1.0	D	0.836	deleterious	None	None	None	None	I
G/K	0.9871	likely_pathogenic	0.9953	pathogenic	-0.968	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	I
G/L	0.987	likely_pathogenic	0.9951	pathogenic	-0.644	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	I
G/M	0.9923	likely_pathogenic	0.9972	pathogenic	-0.56	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	I
G/N	0.9729	likely_pathogenic	0.9884	pathogenic	-0.619	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	I
G/P	0.9988	likely_pathogenic	0.9995	pathogenic	-0.557	Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	I
G/Q	0.9766	likely_pathogenic	0.9916	pathogenic	-0.959	Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	I
G/R	0.9664	likely_pathogenic	0.987	pathogenic	-0.438	Destabilizing	1.0	D	0.854	deleterious	D	0.617448593	None	None	I
G/S	0.7672	likely_pathogenic	0.8899	pathogenic	-0.733	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	I
G/T	0.9466	likely_pathogenic	0.9805	pathogenic	-0.846	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	I
G/V	0.9768	likely_pathogenic	0.9918	pathogenic	-0.557	Destabilizing	1.0	D	0.823	deleterious	D	0.643793922	None	None	I
G/W	0.9877	likely_pathogenic	0.9951	pathogenic	-1.332	Destabilizing	1.0	D	0.804	deleterious	D	0.643995726	None	None	I
G/Y	0.9871	likely_pathogenic	0.9951	pathogenic	-1.015	Destabilizing	1.0	D	0.828	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.