TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32877	98854;98855;98856	chr2:178539436;178539435;178539434	chr2:179404163;179404162;179404161
N2AB	31236	93931;93932;93933	chr2:178539436;178539435;178539434	chr2:179404163;179404162;179404161
N2A	30309	91150;91151;91152	chr2:178539436;178539435;178539434	chr2:179404163;179404162;179404161
N2B	23812	71659;71660;71661	chr2:178539436;178539435;178539434	chr2:179404163;179404162;179404161
Novex-1	23937	72034;72035;72036	chr2:178539436;178539435;178539434	chr2:179404163;179404162;179404161
Novex-2	24004	72235;72236;72237	chr2:178539436;178539435;178539434	chr2:179404163;179404162;179404161
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: Fn3-127
• Domain position: 83
• Structural Position: 115
• Q(SASA): 0.2458
• 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	0.925	0.668	0.73158712388	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-06	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	0.8929	likely_pathogenic	0.8556	pathogenic	-0.655	Destabilizing	1.0	D	0.785	deleterious	D	0.539833602	None	None	I
G/C	0.9554	likely_pathogenic	0.929	pathogenic	-1.064	Destabilizing	1.0	D	0.879	deleterious	D	0.563724755	None	None	I
G/D	0.9842	likely_pathogenic	0.9774	pathogenic	-0.765	Destabilizing	1.0	D	0.927	deleterious	D	0.529856422	None	None	I
G/E	0.992	likely_pathogenic	0.9882	pathogenic	-0.893	Destabilizing	1.0	D	0.918	deleterious	None	None	None	None	I
G/F	0.9944	likely_pathogenic	0.9924	pathogenic	-1.177	Destabilizing	1.0	D	0.898	deleterious	None	None	None	None	I
G/H	0.9919	likely_pathogenic	0.9878	pathogenic	-0.896	Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	I
G/I	0.9947	likely_pathogenic	0.9923	pathogenic	-0.601	Destabilizing	1.0	D	0.903	deleterious	None	None	None	None	I
G/K	0.9955	likely_pathogenic	0.9936	pathogenic	-1.058	Destabilizing	1.0	D	0.917	deleterious	None	None	None	None	I
G/L	0.9908	likely_pathogenic	0.9872	pathogenic	-0.601	Destabilizing	1.0	D	0.889	deleterious	None	None	None	None	I
G/M	0.9963	likely_pathogenic	0.9946	pathogenic	-0.565	Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	I
G/N	0.9826	likely_pathogenic	0.9754	pathogenic	-0.74	Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	I
G/P	0.9991	likely_pathogenic	0.9987	pathogenic	-0.583	Destabilizing	1.0	D	0.917	deleterious	None	None	None	None	I
G/Q	0.9877	likely_pathogenic	0.9825	pathogenic	-1.022	Destabilizing	1.0	D	0.922	deleterious	None	None	None	None	I
G/R	0.9797	likely_pathogenic	0.9716	pathogenic	-0.609	Destabilizing	1.0	D	0.925	deleterious	D	0.544099563	None	None	I
G/S	0.8019	likely_pathogenic	0.7331	pathogenic	-0.975	Destabilizing	1.0	D	0.875	deleterious	D	0.535705772	None	None	I
G/T	0.9724	likely_pathogenic	0.9615	pathogenic	-1.029	Destabilizing	1.0	D	0.916	deleterious	None	None	None	None	I
G/V	0.9893	likely_pathogenic	0.9848	pathogenic	-0.583	Destabilizing	1.0	D	0.899	deleterious	D	0.534010705	None	None	I
G/W	0.9904	likely_pathogenic	0.9853	pathogenic	-1.335	Destabilizing	1.0	D	0.889	deleterious	None	None	None	None	I
G/Y	0.9922	likely_pathogenic	0.9889	pathogenic	-0.992	Destabilizing	1.0	D	0.897	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.