TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21012	63259;63260;63261	chr2:178588691;178588690;178588689	chr2:179453418;179453417;179453416
N2AB	19371	58336;58337;58338	chr2:178588691;178588690;178588689	chr2:179453418;179453417;179453416
N2A	18444	55555;55556;55557	chr2:178588691;178588690;178588689	chr2:179453418;179453417;179453416
N2B	11947	36064;36065;36066	chr2:178588691;178588690;178588689	chr2:179453418;179453417;179453416
Novex-1	12072	36439;36440;36441	chr2:178588691;178588690;178588689	chr2:179453418;179453417;179453416
Novex-2	12139	36640;36641;36642	chr2:178588691;178588690;178588689	chr2:179453418;179453417;179453416
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Fn3-40
• Domain position: 50
• Structural Position: 67
• Q(SASA): 0.4269
• 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
P/L	rs1476856667	None	0.993	N	0.703	0.448	0.497086342495	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
P/L	rs1476856667	None	0.993	N	0.703	0.448	0.497086342495	gnomAD-4.0.0	6.41017E-06	None	None	None	None	N	None	1.69239E-05	0	None	0	0	None	0	0	9.57919E-06	0	0
P/S	None	None	0.955	N	0.595	0.259	0.378498632473	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	6.33473E-05	0	None	0	0	None	0	0	1.3125E-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
P/A	0.0528	likely_benign	0.0584	benign	-1.054	Destabilizing	0.117	N	0.305	neutral	N	0.484520944	None	None	N
P/C	0.4296	ambiguous	0.4465	ambiguous	-0.546	Destabilizing	1.0	D	0.748	deleterious	None	None	None	None	N
P/D	0.7471	likely_pathogenic	0.6909	pathogenic	-1.115	Destabilizing	0.998	D	0.74	deleterious	None	None	None	None	N
P/E	0.5193	ambiguous	0.4664	ambiguous	-1.201	Destabilizing	0.995	D	0.673	neutral	None	None	None	None	N
P/F	0.542	ambiguous	0.536	ambiguous	-1.074	Destabilizing	1.0	D	0.77	deleterious	None	None	None	None	N
P/G	0.3338	likely_benign	0.3125	benign	-1.264	Destabilizing	0.966	D	0.595	neutral	None	None	None	None	N
P/H	0.2845	likely_benign	0.2737	benign	-0.901	Destabilizing	1.0	D	0.732	prob.delet.	N	0.471783177	None	None	N
P/I	0.2845	likely_benign	0.264	benign	-0.616	Destabilizing	0.995	D	0.778	deleterious	None	None	None	None	N
P/K	0.4647	ambiguous	0.4333	ambiguous	-0.987	Destabilizing	0.995	D	0.681	prob.neutral	None	None	None	None	N
P/L	0.1223	likely_benign	0.1178	benign	-0.616	Destabilizing	0.993	D	0.703	prob.neutral	N	0.501279908	None	None	N
P/M	0.2526	likely_benign	0.2374	benign	-0.361	Destabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	N
P/N	0.3974	ambiguous	0.3756	ambiguous	-0.593	Destabilizing	0.998	D	0.761	deleterious	None	None	None	None	N
P/Q	0.1833	likely_benign	0.1772	benign	-0.872	Destabilizing	0.998	D	0.766	deleterious	None	None	None	None	N
P/R	0.2948	likely_benign	0.2795	benign	-0.363	Destabilizing	0.997	D	0.757	deleterious	N	0.458315777	None	None	N
P/S	0.1271	likely_benign	0.1305	benign	-0.928	Destabilizing	0.955	D	0.595	neutral	N	0.485366306	None	None	N
P/T	0.1073	likely_benign	0.1014	benign	-0.927	Destabilizing	0.993	D	0.666	neutral	N	0.466337828	None	None	N
P/V	0.1689	likely_benign	0.1574	benign	-0.727	Destabilizing	0.99	D	0.656	neutral	None	None	None	None	N
P/W	0.7459	likely_pathogenic	0.7244	pathogenic	-1.201	Destabilizing	1.0	D	0.759	deleterious	None	None	None	None	N
P/Y	0.5156	ambiguous	0.4851	ambiguous	-0.942	Destabilizing	1.0	D	0.767	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.