TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25941	78046;78047;78048	chr2:178568311;178568310;178568309	chr2:179433038;179433037;179433036
N2AB	24300	73123;73124;73125	chr2:178568311;178568310;178568309	chr2:179433038;179433037;179433036
N2A	23373	70342;70343;70344	chr2:178568311;178568310;178568309	chr2:179433038;179433037;179433036
N2B	16876	50851;50852;50853	chr2:178568311;178568310;178568309	chr2:179433038;179433037;179433036
Novex-1	17001	51226;51227;51228	chr2:178568311;178568310;178568309	chr2:179433038;179433037;179433036
Novex-2	17068	51427;51428;51429	chr2:178568311;178568310;178568309	chr2:179433038;179433037;179433036
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Fn3-76
• Domain position: 52
• Structural Position: 68
• Q(SASA): 0.2448
• 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
V/I	rs928158833	None	0.981	N	0.445	0.208	0.594705806306	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
V/I	rs928158833	None	0.981	N	0.445	0.208	0.594705806306	gnomAD-4.0.0	3.04526E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	3.61504E-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
V/A	0.5173	ambiguous	0.5261	ambiguous	-1.125	Destabilizing	0.998	D	0.483	neutral	N	0.478699392	None	None	I
V/C	0.899	likely_pathogenic	0.9018	pathogenic	-1.023	Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	I
V/D	0.9838	likely_pathogenic	0.9846	pathogenic	-0.639	Destabilizing	1.0	D	0.828	deleterious	D	0.52439133	None	None	I
V/E	0.9485	likely_pathogenic	0.9518	pathogenic	-0.628	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	I
V/F	0.6236	likely_pathogenic	0.614	pathogenic	-0.778	Destabilizing	0.999	D	0.813	deleterious	N	0.505727189	None	None	I
V/G	0.8675	likely_pathogenic	0.874	pathogenic	-1.433	Destabilizing	1.0	D	0.793	deleterious	D	0.524644819	None	None	I
V/H	0.9792	likely_pathogenic	0.9785	pathogenic	-0.835	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	I
V/I	0.0842	likely_benign	0.0828	benign	-0.392	Destabilizing	0.981	D	0.445	neutral	N	0.467316633	None	None	I
V/K	0.9752	likely_pathogenic	0.9767	pathogenic	-1.006	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	I
V/L	0.4947	ambiguous	0.4838	ambiguous	-0.392	Destabilizing	0.434	N	0.276	neutral	D	0.523751336	None	None	I
V/M	0.45	ambiguous	0.4404	ambiguous	-0.484	Destabilizing	0.999	D	0.723	prob.delet.	None	None	None	None	I
V/N	0.9402	likely_pathogenic	0.9394	pathogenic	-0.932	Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	I
V/P	0.9737	likely_pathogenic	0.9803	pathogenic	-0.6	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	I
V/Q	0.9422	likely_pathogenic	0.9409	pathogenic	-1.015	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	I
V/R	0.9664	likely_pathogenic	0.9685	pathogenic	-0.564	Destabilizing	1.0	D	0.822	deleterious	None	None	None	None	I
V/S	0.7952	likely_pathogenic	0.7932	pathogenic	-1.483	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	I
V/T	0.6337	likely_pathogenic	0.6364	pathogenic	-1.343	Destabilizing	0.998	D	0.527	neutral	None	None	None	None	I
V/W	0.9918	likely_pathogenic	0.9922	pathogenic	-0.946	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	I
V/Y	0.9543	likely_pathogenic	0.9538	pathogenic	-0.636	Destabilizing	1.0	D	0.818	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.