TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30703	92332;92333;92334	chr2:178549615;178549614;178549613	chr2:179414342;179414341;179414340
N2AB	29062	87409;87410;87411	chr2:178549615;178549614;178549613	chr2:179414342;179414341;179414340
N2A	28135	84628;84629;84630	chr2:178549615;178549614;178549613	chr2:179414342;179414341;179414340
N2B	21638	65137;65138;65139	chr2:178549615;178549614;178549613	chr2:179414342;179414341;179414340
Novex-1	21763	65512;65513;65514	chr2:178549615;178549614;178549613	chr2:179414342;179414341;179414340
Novex-2	21830	65713;65714;65715	chr2:178549615;178549614;178549613	chr2:179414342;179414341;179414340
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: Fn3-111
• Domain position: 85
• Structural Position: 118
• Q(SASA): 0.1469
• 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	rs1418904114	-0.671	0.96	D	0.917	0.567	0.670013592873	gnomAD-2.1.1	4.04E-06	None	None	None	None	I	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
G/R	rs1418904114	-0.671	0.96	D	0.917	0.567	0.670013592873	gnomAD-4.0.0	1.59157E-06	None	None	None	None	I	None	0	2.28666E-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	0.6454	likely_pathogenic	0.5007	ambiguous	-0.72	Destabilizing	0.775	D	0.7	prob.neutral	D	0.54896877	None	None	I
G/C	0.889	likely_pathogenic	0.7735	pathogenic	-1.077	Destabilizing	0.995	D	0.85	deleterious	D	0.561339034	None	None	I
G/D	0.9799	likely_pathogenic	0.9669	pathogenic	-1.042	Destabilizing	0.924	D	0.847	deleterious	D	0.560832055	None	None	I
G/E	0.9862	likely_pathogenic	0.9774	pathogenic	-1.142	Destabilizing	0.941	D	0.917	deleterious	None	None	None	None	I
G/F	0.9965	likely_pathogenic	0.9939	pathogenic	-1.146	Destabilizing	0.996	D	0.923	deleterious	None	None	None	None	I
G/H	0.9928	likely_pathogenic	0.986	pathogenic	-1.102	Destabilizing	0.996	D	0.885	deleterious	None	None	None	None	I
G/I	0.9931	likely_pathogenic	0.9855	pathogenic	-0.531	Destabilizing	0.992	D	0.924	deleterious	None	None	None	None	I
G/K	0.9975	likely_pathogenic	0.9954	pathogenic	-1.159	Destabilizing	0.941	D	0.92	deleterious	None	None	None	None	I
G/L	0.9906	likely_pathogenic	0.9803	pathogenic	-0.531	Destabilizing	0.97	D	0.919	deleterious	None	None	None	None	I
G/M	0.9921	likely_pathogenic	0.9839	pathogenic	-0.511	Destabilizing	0.999	D	0.873	deleterious	None	None	None	None	I
G/N	0.9696	likely_pathogenic	0.9441	pathogenic	-0.832	Destabilizing	0.941	D	0.832	deleterious	None	None	None	None	I
G/P	0.9984	likely_pathogenic	0.9976	pathogenic	-0.556	Destabilizing	0.97	D	0.913	deleterious	None	None	None	None	I
G/Q	0.9878	likely_pathogenic	0.9799	pathogenic	-1.096	Destabilizing	0.992	D	0.911	deleterious	None	None	None	None	I
G/R	0.9929	likely_pathogenic	0.9874	pathogenic	-0.773	Destabilizing	0.96	D	0.917	deleterious	D	0.559818097	None	None	I
G/S	0.2643	likely_benign	0.1794	benign	-1.073	Destabilizing	0.048	N	0.656	neutral	N	0.492226068	None	None	I
G/T	0.886	likely_pathogenic	0.7822	pathogenic	-1.102	Destabilizing	0.941	D	0.901	deleterious	None	None	None	None	I
G/V	0.983	likely_pathogenic	0.9635	pathogenic	-0.556	Destabilizing	0.96	D	0.916	deleterious	D	0.560832055	None	None	I
G/W	0.9921	likely_pathogenic	0.987	pathogenic	-1.362	Destabilizing	0.999	D	0.863	deleterious	None	None	None	None	I
G/Y	0.9949	likely_pathogenic	0.9898	pathogenic	-0.999	Destabilizing	0.996	D	0.917	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.