TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16732	50419;50420;50421	chr2:178612331;178612330;178612329	chr2:179477058;179477057;179477056
N2AB	15091	45496;45497;45498	chr2:178612331;178612330;178612329	chr2:179477058;179477057;179477056
N2A	14164	42715;42716;42717	chr2:178612331;178612330;178612329	chr2:179477058;179477057;179477056
N2B	7667	23224;23225;23226	chr2:178612331;178612330;178612329	chr2:179477058;179477057;179477056
Novex-1	7792	23599;23600;23601	chr2:178612331;178612330;178612329	chr2:179477058;179477057;179477056
Novex-2	7859	23800;23801;23802	chr2:178612331;178612330;178612329	chr2:179477058;179477057;179477056
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: Fn3-9
• Domain position: 82
• Structural Position: 115
• Q(SASA): 0.178
• 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	rs1419646565	-0.449	1.0	D	0.927	0.736	0.857878773519	gnomAD-2.1.1	4.04E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.92E-06	0
G/R	rs1419646565	-0.449	1.0	D	0.927	0.736	0.857878773519	gnomAD-4.0.0	1.59388E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.86239E-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	0.9089	likely_pathogenic	0.884	pathogenic	-0.732	Destabilizing	1.0	D	0.767	deleterious	D	0.823066689	None	None	I
G/C	0.9685	likely_pathogenic	0.9564	pathogenic	-1.011	Destabilizing	1.0	D	0.883	deleterious	None	None	None	None	I
G/D	0.9903	likely_pathogenic	0.9867	pathogenic	-1.279	Destabilizing	1.0	D	0.926	deleterious	None	None	None	None	I
G/E	0.992	likely_pathogenic	0.989	pathogenic	-1.417	Destabilizing	1.0	D	0.917	deleterious	D	0.823066689	None	None	I
G/F	0.9949	likely_pathogenic	0.9938	pathogenic	-1.303	Destabilizing	1.0	D	0.902	deleterious	None	None	None	None	I
G/H	0.9955	likely_pathogenic	0.9931	pathogenic	-0.987	Destabilizing	1.0	D	0.882	deleterious	None	None	None	None	I
G/I	0.9965	likely_pathogenic	0.9956	pathogenic	-0.687	Destabilizing	1.0	D	0.907	deleterious	None	None	None	None	I
G/K	0.996	likely_pathogenic	0.9945	pathogenic	-1.227	Destabilizing	1.0	D	0.915	deleterious	None	None	None	None	I
G/L	0.9931	likely_pathogenic	0.9921	pathogenic	-0.687	Destabilizing	1.0	D	0.888	deleterious	None	None	None	None	I
G/M	0.9972	likely_pathogenic	0.9962	pathogenic	-0.496	Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	I
G/N	0.9898	likely_pathogenic	0.9836	pathogenic	-0.868	Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	I
G/P	0.9993	likely_pathogenic	0.9991	pathogenic	-0.666	Destabilizing	1.0	D	0.917	deleterious	None	None	None	None	I
G/Q	0.9903	likely_pathogenic	0.9853	pathogenic	-1.21	Destabilizing	1.0	D	0.924	deleterious	None	None	None	None	I
G/R	0.9861	likely_pathogenic	0.9796	pathogenic	-0.679	Destabilizing	1.0	D	0.927	deleterious	D	0.771760824	None	None	I
G/S	0.8655	likely_pathogenic	0.8123	pathogenic	-1.029	Destabilizing	1.0	D	0.864	deleterious	None	None	None	None	I
G/T	0.979	likely_pathogenic	0.9683	pathogenic	-1.111	Destabilizing	1.0	D	0.915	deleterious	None	None	None	None	I
G/V	0.9924	likely_pathogenic	0.9904	pathogenic	-0.666	Destabilizing	1.0	D	0.899	deleterious	D	0.736435212	None	None	I
G/W	0.9936	likely_pathogenic	0.9914	pathogenic	-1.462	Destabilizing	1.0	D	0.891	deleterious	None	None	None	None	I
G/Y	0.9946	likely_pathogenic	0.9926	pathogenic	-1.14	Destabilizing	1.0	D	0.902	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.