TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6599	20020;20021;20022	chr2:178727783;178727782;178727781	chr2:179592510;179592509;179592508
N2AB	6282	19069;19070;19071	chr2:178727783;178727782;178727781	chr2:179592510;179592509;179592508
N2A	5355	16288;16289;16290	chr2:178727783;178727782;178727781	chr2:179592510;179592509;179592508
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-50
• Domain position: 26
• Structural Position: 40
• Q(SASA): 0.2762
• 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	None	None	1.0	D	0.811	0.723	0.705268275649	gnomAD-4.0.0	2.40064E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.625E-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	0.7838	likely_pathogenic	0.8648	pathogenic	-0.266	Destabilizing	1.0	D	0.773	deleterious	D	0.573448032	None	None	I
G/C	0.974	likely_pathogenic	0.989	pathogenic	-0.808	Destabilizing	1.0	D	0.7	prob.neutral	None	None	None	None	I
G/D	0.9826	likely_pathogenic	0.9923	pathogenic	-0.505	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	I
G/E	0.9878	likely_pathogenic	0.995	pathogenic	-0.621	Destabilizing	1.0	D	0.811	deleterious	D	0.627149506	None	None	I
G/F	0.9966	likely_pathogenic	0.998	pathogenic	-0.817	Destabilizing	1.0	D	0.75	deleterious	None	None	None	None	I
G/H	0.9983	likely_pathogenic	0.9993	pathogenic	-0.581	Destabilizing	1.0	D	0.68	prob.neutral	None	None	None	None	I
G/I	0.9894	likely_pathogenic	0.9947	pathogenic	-0.232	Destabilizing	1.0	D	0.767	deleterious	None	None	None	None	I
G/K	0.9972	likely_pathogenic	0.9989	pathogenic	-0.878	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	I
G/L	0.9937	likely_pathogenic	0.9966	pathogenic	-0.232	Destabilizing	1.0	D	0.784	deleterious	None	None	None	None	I
G/M	0.9954	likely_pathogenic	0.9976	pathogenic	-0.464	Destabilizing	1.0	D	0.691	prob.neutral	None	None	None	None	I
G/N	0.9924	likely_pathogenic	0.9966	pathogenic	-0.543	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	I
G/P	0.9985	likely_pathogenic	0.9993	pathogenic	-0.207	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	I
G/Q	0.9965	likely_pathogenic	0.9986	pathogenic	-0.742	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	I
G/R	0.9931	likely_pathogenic	0.9972	pathogenic	-0.516	Destabilizing	1.0	D	0.801	deleterious	D	0.646801344	None	None	I
G/S	0.887	likely_pathogenic	0.9501	pathogenic	-0.714	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	I
G/T	0.9771	likely_pathogenic	0.9899	pathogenic	-0.748	Destabilizing	1.0	D	0.808	deleterious	None	None	None	None	I
G/V	0.9664	likely_pathogenic	0.9839	pathogenic	-0.207	Destabilizing	1.0	D	0.783	deleterious	D	0.630781983	None	None	I
G/W	0.9933	likely_pathogenic	0.9969	pathogenic	-1.061	Destabilizing	1.0	D	0.695	prob.neutral	None	None	None	None	I
G/Y	0.9942	likely_pathogenic	0.9974	pathogenic	-0.669	Destabilizing	1.0	D	0.737	prob.delet.	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.