TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18455	55588;55589;55590	chr2:178601727;178601726;178601725	chr2:179466454;179466453;179466452
N2AB	16814	50665;50666;50667	chr2:178601727;178601726;178601725	chr2:179466454;179466453;179466452
N2A	15887	47884;47885;47886	chr2:178601727;178601726;178601725	chr2:179466454;179466453;179466452
N2B	9390	28393;28394;28395	chr2:178601727;178601726;178601725	chr2:179466454;179466453;179466452
Novex-1	9515	28768;28769;28770	chr2:178601727;178601726;178601725	chr2:179466454;179466453;179466452
Novex-2	9582	28969;28970;28971	chr2:178601727;178601726;178601725	chr2:179466454;179466453;179466452
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-115
• Domain position: 74
• Structural Position: 152
• Q(SASA): 0.1744
• 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/V	rs2154193105	None	1.0	D	0.75	0.757	0.803425027574	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
G/V	rs2154193105	None	1.0	D	0.75	0.757	0.803425027574	gnomAD-4.0.0	6.57583E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.47137E-05	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	0.816	likely_pathogenic	0.8017	pathogenic	-0.364	Destabilizing	1.0	D	0.68	prob.neutral	D	0.574005238	None	None	I
G/C	0.9741	likely_pathogenic	0.9718	pathogenic	-0.533	Destabilizing	1.0	D	0.723	prob.delet.	D	0.602368609	None	None	I
G/D	0.9902	likely_pathogenic	0.9882	pathogenic	-0.913	Destabilizing	1.0	D	0.78	deleterious	D	0.601965001	None	None	I
G/E	0.9945	likely_pathogenic	0.9939	pathogenic	-0.837	Destabilizing	1.0	D	0.768	deleterious	None	None	None	None	I
G/F	0.9982	likely_pathogenic	0.998	pathogenic	-0.514	Destabilizing	1.0	D	0.742	deleterious	None	None	None	None	I
G/H	0.9972	likely_pathogenic	0.997	pathogenic	-1.366	Destabilizing	1.0	D	0.707	prob.neutral	None	None	None	None	I
G/I	0.9982	likely_pathogenic	0.9981	pathogenic	0.437	Stabilizing	1.0	D	0.75	deleterious	None	None	None	None	I
G/K	0.9955	likely_pathogenic	0.9957	pathogenic	-0.649	Destabilizing	1.0	D	0.769	deleterious	None	None	None	None	I
G/L	0.9958	likely_pathogenic	0.9951	pathogenic	0.437	Stabilizing	1.0	D	0.745	deleterious	None	None	None	None	I
G/M	0.9979	likely_pathogenic	0.9974	pathogenic	0.244	Stabilizing	1.0	D	0.722	prob.delet.	None	None	None	None	I
G/N	0.9921	likely_pathogenic	0.9896	pathogenic	-0.601	Destabilizing	1.0	D	0.798	deleterious	None	None	None	None	I
G/P	0.9993	likely_pathogenic	0.9995	pathogenic	0.215	Stabilizing	1.0	D	0.761	deleterious	None	None	None	None	I
G/Q	0.9914	likely_pathogenic	0.9914	pathogenic	-0.543	Destabilizing	1.0	D	0.768	deleterious	None	None	None	None	I
G/R	0.9836	likely_pathogenic	0.986	pathogenic	-0.757	Destabilizing	1.0	D	0.775	deleterious	D	0.602166805	None	None	I
G/S	0.8307	likely_pathogenic	0.8172	pathogenic	-0.971	Destabilizing	1.0	D	0.795	deleterious	D	0.585743835	None	None	I
G/T	0.9879	likely_pathogenic	0.9858	pathogenic	-0.783	Destabilizing	1.0	D	0.77	deleterious	None	None	None	None	I
G/V	0.9942	likely_pathogenic	0.9942	pathogenic	0.215	Stabilizing	1.0	D	0.75	deleterious	D	0.602368609	None	None	I
G/W	0.9952	likely_pathogenic	0.9955	pathogenic	-1.169	Destabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	I
G/Y	0.9975	likely_pathogenic	0.9974	pathogenic	-0.551	Destabilizing	1.0	D	0.739	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.