TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30802	92629;92630;92631	chr2:178549222;178549221;178549220	chr2:179413949;179413948;179413947
N2AB	29161	87706;87707;87708	chr2:178549222;178549221;178549220	chr2:179413949;179413948;179413947
N2A	28234	84925;84926;84927	chr2:178549222;178549221;178549220	chr2:179413949;179413948;179413947
N2B	21737	65434;65435;65436	chr2:178549222;178549221;178549220	chr2:179413949;179413948;179413947
Novex-1	21862	65809;65810;65811	chr2:178549222;178549221;178549220	chr2:179413949;179413948;179413947
Novex-2	21929	66010;66011;66012	chr2:178549222;178549221;178549220	chr2:179413949;179413948;179413947
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: Fn3-112
• Domain position: 84
• Structural Position: 115
• Q(SASA): 0.2489
• 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	rs1698367521	None	1.0	D	0.926	0.759	0.777634074098	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	6.55E-05	0	0	0	None	0	0	0	0	0
G/E	rs1698367521	None	1.0	D	0.926	0.759	0.777634074098	gnomAD-4.0.0	6.57237E-06	None	None	None	None	I	None	0	6.5548E-05	None	0	0	None	0	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	0.8069	likely_pathogenic	0.7927	pathogenic	-0.61	Destabilizing	1.0	D	0.777	deleterious	D	0.566000296	None	None	I
G/C	0.928	likely_pathogenic	0.9269	pathogenic	-1.006	Destabilizing	1.0	D	0.885	deleterious	None	None	None	None	I
G/D	0.9503	likely_pathogenic	0.956	pathogenic	-1.083	Destabilizing	1.0	D	0.932	deleterious	None	None	None	None	I
G/E	0.9689	likely_pathogenic	0.97	pathogenic	-1.243	Destabilizing	1.0	D	0.926	deleterious	D	0.584104551	None	None	I
G/F	0.9922	likely_pathogenic	0.9921	pathogenic	-1.248	Destabilizing	1.0	D	0.906	deleterious	None	None	None	None	I
G/H	0.9784	likely_pathogenic	0.9786	pathogenic	-0.817	Destabilizing	1.0	D	0.888	deleterious	None	None	None	None	I
G/I	0.9899	likely_pathogenic	0.9886	pathogenic	-0.684	Destabilizing	1.0	D	0.911	deleterious	None	None	None	None	I
G/K	0.9693	likely_pathogenic	0.9692	pathogenic	-1.148	Destabilizing	1.0	D	0.925	deleterious	None	None	None	None	I
G/L	0.9846	likely_pathogenic	0.9851	pathogenic	-0.684	Destabilizing	1.0	D	0.897	deleterious	None	None	None	None	I
G/M	0.9892	likely_pathogenic	0.9888	pathogenic	-0.573	Destabilizing	1.0	D	0.884	deleterious	None	None	None	None	I
G/N	0.9675	likely_pathogenic	0.9684	pathogenic	-0.797	Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	I
G/P	0.9984	likely_pathogenic	0.9984	pathogenic	-0.625	Destabilizing	1.0	D	0.925	deleterious	None	None	None	None	I
G/Q	0.9622	likely_pathogenic	0.962	pathogenic	-1.142	Destabilizing	1.0	D	0.931	deleterious	None	None	None	None	I
G/R	0.9283	likely_pathogenic	0.9244	pathogenic	-0.587	Destabilizing	1.0	D	0.934	deleterious	D	0.572837151	None	None	I
G/S	0.7157	likely_pathogenic	0.7051	pathogenic	-0.919	Destabilizing	1.0	D	0.872	deleterious	None	None	None	None	I
G/T	0.9371	likely_pathogenic	0.9342	pathogenic	-1.022	Destabilizing	1.0	D	0.925	deleterious	None	None	None	None	I
G/V	0.973	likely_pathogenic	0.9695	pathogenic	-0.625	Destabilizing	1.0	D	0.907	deleterious	D	0.545111337	None	None	I
G/W	0.9822	likely_pathogenic	0.9819	pathogenic	-1.375	Destabilizing	1.0	D	0.896	deleterious	None	None	None	None	I
G/Y	0.9848	likely_pathogenic	0.9858	pathogenic	-1.063	Destabilizing	1.0	D	0.905	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.