TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8148	24667;24668;24669	chr2:178718758;178718757;178718756	chr2:179583485;179583484;179583483
N2AB	7831	23716;23717;23718	chr2:178718758;178718757;178718756	chr2:179583485;179583484;179583483
N2A	6904	20935;20936;20937	chr2:178718758;178718757;178718756	chr2:179583485;179583484;179583483
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: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Ig-66
• Domain position: 71
• Structural Position: 154
• Q(SASA): 0.0942
• Predicted PPI site: N

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
Y/C	rs1236449802	-0.866	1.0	D	0.837	0.901	0.898236699851	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.89E-06	0
Y/C	rs1236449802	-0.866	1.0	D	0.837	0.901	0.898236699851	gnomAD-4.0.0	4.10528E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.39694E-06	0	0
Y/N	None	None	1.0	D	0.857	0.892	0.930053955015	gnomAD-4.0.0	1.59133E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85851E-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
Y/A	0.9803	likely_pathogenic	0.9841	pathogenic	-2.196	Highly Destabilizing	1.0	D	0.826	deleterious	None	None	None	None	N
Y/C	0.8157	likely_pathogenic	0.8468	pathogenic	-1.766	Destabilizing	1.0	D	0.837	deleterious	D	0.652494737	None	None	N
Y/D	0.9915	likely_pathogenic	0.9928	pathogenic	-2.72	Highly Destabilizing	1.0	D	0.861	deleterious	D	0.652494737	None	None	N
Y/E	0.9967	likely_pathogenic	0.9971	pathogenic	-2.47	Highly Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
Y/F	0.1116	likely_benign	0.1188	benign	-0.751	Destabilizing	0.999	D	0.697	prob.neutral	D	0.577607354	None	None	N
Y/G	0.9777	likely_pathogenic	0.9818	pathogenic	-2.655	Highly Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
Y/H	0.9077	likely_pathogenic	0.9297	pathogenic	-2.048	Highly Destabilizing	1.0	D	0.786	deleterious	D	0.652292933	None	None	N
Y/I	0.7609	likely_pathogenic	0.7782	pathogenic	-0.682	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
Y/K	0.9941	likely_pathogenic	0.995	pathogenic	-1.755	Destabilizing	1.0	D	0.864	deleterious	None	None	None	None	N
Y/L	0.7489	likely_pathogenic	0.7769	pathogenic	-0.682	Destabilizing	0.999	D	0.759	deleterious	None	None	None	None	N
Y/M	0.9363	likely_pathogenic	0.9465	pathogenic	-0.901	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
Y/N	0.9482	likely_pathogenic	0.9588	pathogenic	-2.636	Highly Destabilizing	1.0	D	0.857	deleterious	D	0.652494737	None	None	N
Y/P	0.997	likely_pathogenic	0.9972	pathogenic	-1.202	Destabilizing	1.0	D	0.882	deleterious	None	None	None	None	N
Y/Q	0.9942	likely_pathogenic	0.9955	pathogenic	-2.188	Highly Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
Y/R	0.9795	likely_pathogenic	0.9828	pathogenic	-2.032	Highly Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	N
Y/S	0.9505	likely_pathogenic	0.9618	pathogenic	-3.004	Highly Destabilizing	1.0	D	0.863	deleterious	D	0.652494737	None	None	N
Y/T	0.9745	likely_pathogenic	0.9788	pathogenic	-2.602	Highly Destabilizing	1.0	D	0.866	deleterious	None	None	None	None	N
Y/V	0.7005	likely_pathogenic	0.7258	pathogenic	-1.202	Destabilizing	1.0	D	0.79	deleterious	None	None	None	None	N
Y/W	0.7856	likely_pathogenic	0.8043	pathogenic	-0.123	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	N

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.