TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8166	24721;24722;24723	chr2:178718704;178718703;178718702	chr2:179583431;179583430;179583429
N2AB	7849	23770;23771;23772	chr2:178718704;178718703;178718702	chr2:179583431;179583430;179583429
N2A	6922	20989;20990;20991	chr2:178718704;178718703;178718702	chr2:179583431;179583430;179583429
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: F
• RefSeq wild type transcript codon: TTT
• RefSeq wild type template codon: AAA
• Domain: Ig-66
• Domain position: 89
• Structural Position: 175
• Q(SASA): 0.5182
• 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
F/L	None	None	None	N	0.069	0.17	0.26547132957	gnomAD-4.0.0	1.59266E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86121E-06	0	0
F/S	None	None	0.021	N	0.219	0.182	0.592052101994	gnomAD-4.0.0	6.84458E-07	None	None	None	None	N	None	2.98882E-05	0	None	0	0	None	0	0	0	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
F/A	0.2783	likely_benign	0.3275	benign	-1.666	Destabilizing	0.061	N	0.355	neutral	None	None	None	None	N
F/C	0.3861	ambiguous	0.3902	ambiguous	-0.718	Destabilizing	0.921	D	0.36	neutral	N	0.48570601	None	None	N
F/D	0.5402	ambiguous	0.5971	pathogenic	0.357	Stabilizing	0.418	N	0.477	neutral	None	None	None	None	N
F/E	0.59	likely_pathogenic	0.6329	pathogenic	0.392	Stabilizing	0.418	N	0.469	neutral	None	None	None	None	N
F/G	0.6135	likely_pathogenic	0.7051	pathogenic	-1.941	Destabilizing	0.418	N	0.452	neutral	None	None	None	None	N
F/H	0.3161	likely_benign	0.3212	benign	-0.181	Destabilizing	0.94	D	0.38	neutral	None	None	None	None	N
F/I	0.148	likely_benign	0.1689	benign	-0.892	Destabilizing	0.002	N	0.101	neutral	N	0.467237197	None	None	N
F/K	0.5702	likely_pathogenic	0.6211	pathogenic	-0.598	Destabilizing	0.418	N	0.461	neutral	None	None	None	None	N
F/L	0.6259	likely_pathogenic	0.6776	pathogenic	-0.892	Destabilizing	None	N	0.069	neutral	N	0.448286077	None	None	N
F/M	0.3808	ambiguous	0.4261	ambiguous	-0.665	Destabilizing	0.716	D	0.318	neutral	None	None	None	None	N
F/N	0.3515	ambiguous	0.4065	ambiguous	-0.531	Destabilizing	0.418	N	0.453	neutral	None	None	None	None	N
F/P	0.963	likely_pathogenic	0.9748	pathogenic	-1.136	Destabilizing	0.836	D	0.433	neutral	None	None	None	None	N
F/Q	0.4811	ambiguous	0.5209	ambiguous	-0.613	Destabilizing	0.836	D	0.427	neutral	None	None	None	None	N
F/R	0.416	ambiguous	0.4529	ambiguous	0.027	Stabilizing	0.836	D	0.443	neutral	None	None	None	None	N
F/S	0.1648	likely_benign	0.199	benign	-1.386	Destabilizing	0.021	N	0.219	neutral	N	0.457481563	None	None	N
F/T	0.2054	likely_benign	0.2481	benign	-1.262	Destabilizing	0.004	N	0.16	neutral	None	None	None	None	N
F/V	0.1532	likely_benign	0.1697	benign	-1.136	Destabilizing	0.017	N	0.327	neutral	N	0.491114134	None	None	N
F/W	0.4136	ambiguous	0.4495	ambiguous	-0.194	Destabilizing	0.983	D	0.364	neutral	None	None	None	None	N
F/Y	0.1317	likely_benign	0.1364	benign	-0.343	Destabilizing	0.523	D	0.311	neutral	N	0.49827218	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.