TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23808	71647;71648;71649	chr2:178574710;178574709;178574708	chr2:179439437;179439436;179439435
N2AB	22167	66724;66725;66726	chr2:178574710;178574709;178574708	chr2:179439437;179439436;179439435
N2A	21240	63943;63944;63945	chr2:178574710;178574709;178574708	chr2:179439437;179439436;179439435
N2B	14743	44452;44453;44454	chr2:178574710;178574709;178574708	chr2:179439437;179439436;179439435
Novex-1	14868	44827;44828;44829	chr2:178574710;178574709;178574708	chr2:179439437;179439436;179439435
Novex-2	14935	45028;45029;45030	chr2:178574710;178574709;178574708	chr2:179439437;179439436;179439435
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: Fn3-60
• Domain position: 83
• Structural Position: 115
• Q(SASA): 0.1857
• 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/R	None	None	1.0	D	0.923	0.726	0.62360313169	gnomAD-4.0.0	6.84393E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99622E-07	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	0.9262	likely_pathogenic	0.9047	pathogenic	-0.639	Destabilizing	1.0	D	0.759	deleterious	D	0.534481685	None	None	I
G/C	0.9798	likely_pathogenic	0.9735	pathogenic	-1.0	Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	I
G/D	0.9876	likely_pathogenic	0.9832	pathogenic	-0.959	Destabilizing	1.0	D	0.922	deleterious	None	None	None	None	I
G/E	0.9942	likely_pathogenic	0.9916	pathogenic	-1.084	Destabilizing	1.0	D	0.915	deleterious	D	0.557701275	None	None	I
G/F	0.9973	likely_pathogenic	0.9959	pathogenic	-1.096	Destabilizing	1.0	D	0.899	deleterious	None	None	None	None	I
G/H	0.9944	likely_pathogenic	0.9918	pathogenic	-0.91	Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	I
G/I	0.9971	likely_pathogenic	0.9954	pathogenic	-0.564	Destabilizing	1.0	D	0.902	deleterious	None	None	None	None	I
G/K	0.9941	likely_pathogenic	0.991	pathogenic	-1.218	Destabilizing	1.0	D	0.913	deleterious	None	None	None	None	I
G/L	0.9954	likely_pathogenic	0.9927	pathogenic	-0.564	Destabilizing	1.0	D	0.883	deleterious	None	None	None	None	I
G/M	0.9976	likely_pathogenic	0.9961	pathogenic	-0.528	Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	I
G/N	0.9896	likely_pathogenic	0.9836	pathogenic	-0.875	Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	I
G/P	0.9995	likely_pathogenic	0.9991	pathogenic	-0.552	Destabilizing	1.0	D	0.912	deleterious	None	None	None	None	I
G/Q	0.9899	likely_pathogenic	0.9841	pathogenic	-1.155	Destabilizing	1.0	D	0.92	deleterious	None	None	None	None	I
G/R	0.9801	likely_pathogenic	0.9703	pathogenic	-0.716	Destabilizing	1.0	D	0.923	deleterious	D	0.557701275	None	None	I
G/S	0.8731	likely_pathogenic	0.8384	pathogenic	-1.066	Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	I
G/T	0.9838	likely_pathogenic	0.978	pathogenic	-1.125	Destabilizing	1.0	D	0.913	deleterious	None	None	None	None	I
G/V	0.9936	likely_pathogenic	0.9909	pathogenic	-0.552	Destabilizing	1.0	D	0.895	deleterious	D	0.522960796	None	None	I
G/W	0.9953	likely_pathogenic	0.9937	pathogenic	-1.289	Destabilizing	1.0	D	0.888	deleterious	None	None	None	None	I
G/Y	0.9959	likely_pathogenic	0.9932	pathogenic	-0.956	Destabilizing	1.0	D	0.899	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.