TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8064	24415;24416;24417	chr2:178719200;178719199;178719198	chr2:179583927;179583926;179583925
N2AB	7747	23464;23465;23466	chr2:178719200;178719199;178719198	chr2:179583927;179583926;179583925
N2A	6820	20683;20684;20685	chr2:178719200;178719199;178719198	chr2:179583927;179583926;179583925
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: GGT
• RefSeq wild type template codon: CCA
• Domain: Ig-65
• Domain position: 80
• Structural Position: 164
• Q(SASA): 0.2559
• 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/D	None	None	0.45	D	0.545	0.695	0.44440487	gnomAD-4.0.0	1.59145E-06	None	None	None	None	I	None	0	0	None	0	2.77285E-05	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	0.5646	likely_pathogenic	0.6469	pathogenic	-0.329	Destabilizing	0.991	D	0.643	neutral	D	0.60524744	None	None	I
G/C	0.8555	likely_pathogenic	0.8933	pathogenic	-0.91	Destabilizing	1.0	D	0.767	deleterious	D	0.64151514	None	None	I
G/D	0.8228	likely_pathogenic	0.8964	pathogenic	-0.752	Destabilizing	0.45	N	0.545	neutral	D	0.61088014	None	None	I
G/E	0.8625	likely_pathogenic	0.9263	pathogenic	-0.928	Destabilizing	0.996	D	0.779	deleterious	None	None	None	None	I
G/F	0.9578	likely_pathogenic	0.9681	pathogenic	-1.144	Destabilizing	1.0	D	0.806	deleterious	None	None	None	None	I
G/H	0.9321	likely_pathogenic	0.96	pathogenic	-0.526	Destabilizing	1.0	D	0.788	deleterious	None	None	None	None	I
G/I	0.9385	likely_pathogenic	0.9647	pathogenic	-0.561	Destabilizing	1.0	D	0.806	deleterious	None	None	None	None	I
G/K	0.9173	likely_pathogenic	0.9567	pathogenic	-0.803	Destabilizing	0.998	D	0.781	deleterious	None	None	None	None	I
G/L	0.9427	likely_pathogenic	0.9608	pathogenic	-0.561	Destabilizing	0.999	D	0.774	deleterious	None	None	None	None	I
G/M	0.9533	likely_pathogenic	0.9719	pathogenic	-0.534	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	I
G/N	0.8666	likely_pathogenic	0.9185	pathogenic	-0.476	Destabilizing	0.996	D	0.763	deleterious	None	None	None	None	I
G/P	0.9969	likely_pathogenic	0.9977	pathogenic	-0.455	Destabilizing	0.999	D	0.783	deleterious	None	None	None	None	I
G/Q	0.8742	likely_pathogenic	0.9284	pathogenic	-0.799	Destabilizing	0.999	D	0.796	deleterious	None	None	None	None	I
G/R	0.8198	likely_pathogenic	0.8879	pathogenic	-0.317	Destabilizing	0.999	D	0.795	deleterious	D	0.619147	None	None	I
G/S	0.4328	ambiguous	0.5184	ambiguous	-0.573	Destabilizing	0.997	D	0.766	deleterious	D	0.607428	None	None	I
G/T	0.8168	likely_pathogenic	0.8716	pathogenic	-0.69	Destabilizing	0.998	D	0.779	deleterious	None	None	None	None	I
G/V	0.8749	likely_pathogenic	0.9191	pathogenic	-0.455	Destabilizing	0.999	D	0.772	deleterious	D	0.6571309	None	None	I
G/W	0.9446	likely_pathogenic	0.9612	pathogenic	-1.259	Destabilizing	1.0	D	0.759	deleterious	None	None	None	None	I
G/Y	0.9306	likely_pathogenic	0.9561	pathogenic	-0.932	Destabilizing	1.0	D	0.801	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.