TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16502	49729;49730;49731	chr2:178613779;178613778;178613777	chr2:179478506;179478505;179478504
N2AB	14861	44806;44807;44808	chr2:178613779;178613778;178613777	chr2:179478506;179478505;179478504
N2A	13934	42025;42026;42027	chr2:178613779;178613778;178613777	chr2:179478506;179478505;179478504
N2B	7437	22534;22535;22536	chr2:178613779;178613778;178613777	chr2:179478506;179478505;179478504
Novex-1	7562	22909;22910;22911	chr2:178613779;178613778;178613777	chr2:179478506;179478505;179478504
Novex-2	7629	23110;23111;23112	chr2:178613779;178613778;178613777	chr2:179478506;179478505;179478504
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Fn3-7
• Domain position: 53
• Structural Position: 70
• Q(SASA): 0.482
• 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
K/N	None	None	1.0	N	0.683	0.309	0.190952846119	gnomAD-4.0.0	1.59414E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	0	3.03067E-05
K/Q	None	None	1.0	N	0.681	0.369	0.236278675362	gnomAD-4.0.0	1.59412E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	0	3.0303E-05

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
K/A	0.963	likely_pathogenic	0.8609	pathogenic	-0.018	Destabilizing	0.999	D	0.592	neutral	None	None	None	None	I
K/C	0.9878	likely_pathogenic	0.9441	pathogenic	-0.528	Destabilizing	1.0	D	0.685	prob.neutral	None	None	None	None	I
K/D	0.9848	likely_pathogenic	0.9087	pathogenic	-0.381	Destabilizing	1.0	D	0.641	neutral	None	None	None	None	I
K/E	0.957	likely_pathogenic	0.8154	pathogenic	-0.395	Destabilizing	0.999	D	0.582	neutral	N	0.471543224	None	None	I
K/F	0.9951	likely_pathogenic	0.9749	pathogenic	-0.366	Destabilizing	1.0	D	0.651	neutral	None	None	None	None	I
K/G	0.9714	likely_pathogenic	0.8667	pathogenic	-0.14	Destabilizing	1.0	D	0.595	neutral	None	None	None	None	I
K/H	0.8801	likely_pathogenic	0.6657	pathogenic	-0.217	Destabilizing	1.0	D	0.617	neutral	None	None	None	None	I
K/I	0.964	likely_pathogenic	0.8697	pathogenic	0.22	Stabilizing	1.0	D	0.671	neutral	None	None	None	None	I
K/L	0.9394	likely_pathogenic	0.8256	pathogenic	0.22	Stabilizing	1.0	D	0.595	neutral	None	None	None	None	I
K/M	0.936	likely_pathogenic	0.803	pathogenic	-0.154	Destabilizing	1.0	D	0.613	neutral	D	0.542388462	None	None	I
K/N	0.9735	likely_pathogenic	0.8788	pathogenic	-0.104	Destabilizing	1.0	D	0.683	prob.neutral	N	0.479474991	None	None	I
K/P	0.9479	likely_pathogenic	0.8818	pathogenic	0.164	Stabilizing	1.0	D	0.606	neutral	None	None	None	None	I
K/Q	0.8038	likely_pathogenic	0.4951	ambiguous	-0.24	Destabilizing	1.0	D	0.681	prob.neutral	N	0.478251846	None	None	I
K/R	0.1725	likely_benign	0.0992	benign	-0.166	Destabilizing	0.999	D	0.54	neutral	N	0.478157631	None	None	I
K/S	0.9751	likely_pathogenic	0.8766	pathogenic	-0.446	Destabilizing	0.999	D	0.625	neutral	None	None	None	None	I
K/T	0.9193	likely_pathogenic	0.6959	pathogenic	-0.346	Destabilizing	1.0	D	0.637	neutral	N	0.449600555	None	None	I
K/V	0.9476	likely_pathogenic	0.8247	pathogenic	0.164	Stabilizing	1.0	D	0.605	neutral	None	None	None	None	I
K/W	0.9915	likely_pathogenic	0.9495	pathogenic	-0.477	Destabilizing	1.0	D	0.689	prob.neutral	None	None	None	None	I
K/Y	0.9815	likely_pathogenic	0.9213	pathogenic	-0.128	Destabilizing	1.0	D	0.601	neutral	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.