TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6879	20860;20861;20862	chr2:178725569;178725568;178725567	chr2:179590296;179590295;179590294
N2AB	6562	19909;19910;19911	chr2:178725569;178725568;178725567	chr2:179590296;179590295;179590294
N2A	5635	17128;17129;17130	chr2:178725569;178725568;178725567	chr2:179590296;179590295;179590294
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: GGC
• RefSeq wild type template codon: CCG
• Domain: Ig-53
• Domain position: 26
• Structural Position: 40
• Q(SASA): 0.4775
• 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	rs370099653	-0.56	1.0	D	0.796	0.651	None	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
G/D	rs370099653	-0.56	1.0	D	0.796	0.651	None	gnomAD-4.0.0	4.06019E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	4.81986E-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	0.5097	ambiguous	0.5668	pathogenic	-0.542	Destabilizing	1.0	D	0.753	deleterious	D	0.579716478	None	None	I
G/C	0.9048	likely_pathogenic	0.9273	pathogenic	-0.861	Destabilizing	1.0	D	0.707	prob.neutral	D	0.630024768	None	None	I
G/D	0.9151	likely_pathogenic	0.9486	pathogenic	-1.224	Destabilizing	1.0	D	0.796	deleterious	D	0.628813943	None	None	I
G/E	0.9489	likely_pathogenic	0.9664	pathogenic	-1.351	Destabilizing	1.0	D	0.78	deleterious	None	None	None	None	I
G/F	0.9804	likely_pathogenic	0.9843	pathogenic	-1.095	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	I
G/H	0.9872	likely_pathogenic	0.9922	pathogenic	-1.07	Destabilizing	1.0	D	0.677	prob.neutral	None	None	None	None	I
G/I	0.9554	likely_pathogenic	0.961	pathogenic	-0.454	Destabilizing	1.0	D	0.762	deleterious	None	None	None	None	I
G/K	0.9874	likely_pathogenic	0.9919	pathogenic	-1.352	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	I
G/L	0.9702	likely_pathogenic	0.9749	pathogenic	-0.454	Destabilizing	1.0	D	0.769	deleterious	None	None	None	None	I
G/M	0.9755	likely_pathogenic	0.9811	pathogenic	-0.41	Destabilizing	1.0	D	0.692	prob.neutral	None	None	None	None	I
G/N	0.9512	likely_pathogenic	0.9672	pathogenic	-0.901	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	I
G/P	0.9945	likely_pathogenic	0.9959	pathogenic	-0.446	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	I
G/Q	0.9815	likely_pathogenic	0.988	pathogenic	-1.175	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	I
G/R	0.9763	likely_pathogenic	0.9848	pathogenic	-0.877	Destabilizing	1.0	D	0.783	deleterious	D	0.62962116	None	None	I
G/S	0.5842	likely_pathogenic	0.6657	pathogenic	-0.999	Destabilizing	1.0	D	0.808	deleterious	D	0.596977025	None	None	I
G/T	0.8629	likely_pathogenic	0.8985	pathogenic	-1.068	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	I
G/V	0.8948	likely_pathogenic	0.912	pathogenic	-0.446	Destabilizing	1.0	D	0.759	deleterious	D	0.62962116	None	None	I
G/W	0.9696	likely_pathogenic	0.9782	pathogenic	-1.359	Destabilizing	1.0	D	0.691	prob.neutral	None	None	None	None	I
G/Y	0.9695	likely_pathogenic	0.9793	pathogenic	-1.005	Destabilizing	1.0	D	0.736	prob.delet.	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.