TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27561	82906;82907;82908	chr2:178563451;178563450;178563449	chr2:179428178;179428177;179428176
N2AB	25920	77983;77984;77985	chr2:178563451;178563450;178563449	chr2:179428178;179428177;179428176
N2A	24993	75202;75203;75204	chr2:178563451;178563450;178563449	chr2:179428178;179428177;179428176
N2B	18496	55711;55712;55713	chr2:178563451;178563450;178563449	chr2:179428178;179428177;179428176
Novex-1	18621	56086;56087;56088	chr2:178563451;178563450;178563449	chr2:179428178;179428177;179428176
Novex-2	18688	56287;56288;56289	chr2:178563451;178563450;178563449	chr2:179428178;179428177;179428176
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: F
• RefSeq wild type transcript codon: TTC
• RefSeq wild type template codon: AAG
• Domain: Fn3-88
• Domain position: 93
• Structural Position: 126
• Q(SASA): 0.4337
• 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/S	None	None	0.013	N	0.45	0.215	0.641573772263	gnomAD-4.0.0	1.59145E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85843E-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
F/A	0.5387	ambiguous	0.556	ambiguous	-1.901	Destabilizing	0.216	N	0.504	neutral	None	None	None	None	N
F/C	0.3156	likely_benign	0.3321	benign	-0.825	Destabilizing	0.988	D	0.608	neutral	N	0.479883128	None	None	N
F/D	0.8276	likely_pathogenic	0.8232	pathogenic	0.207	Stabilizing	0.824	D	0.663	prob.neutral	None	None	None	None	N
F/E	0.877	likely_pathogenic	0.8719	pathogenic	0.261	Stabilizing	0.571	D	0.668	prob.neutral	None	None	None	None	N
F/G	0.7306	likely_pathogenic	0.7475	pathogenic	-2.189	Highly Destabilizing	0.4	N	0.589	neutral	None	None	None	None	N
F/H	0.5905	likely_pathogenic	0.6016	pathogenic	-0.403	Destabilizing	0.824	D	0.562	neutral	None	None	None	None	N
F/I	0.3935	ambiguous	0.3633	ambiguous	-1.072	Destabilizing	0.335	N	0.404	neutral	N	0.441959458	None	None	N
F/K	0.9105	likely_pathogenic	0.9047	pathogenic	-0.651	Destabilizing	0.571	D	0.661	prob.neutral	None	None	None	None	N
F/L	0.8032	likely_pathogenic	0.8108	pathogenic	-1.072	Destabilizing	0.001	N	0.153	neutral	N	0.450194939	None	None	N
F/M	0.6612	likely_pathogenic	0.6541	pathogenic	-0.789	Destabilizing	0.824	D	0.487	neutral	None	None	None	None	N
F/N	0.6047	likely_pathogenic	0.6332	pathogenic	-0.558	Destabilizing	0.824	D	0.673	prob.neutral	None	None	None	None	N
F/P	0.6985	likely_pathogenic	0.7372	pathogenic	-1.337	Destabilizing	0.905	D	0.673	prob.neutral	None	None	None	None	N
F/Q	0.8156	likely_pathogenic	0.8164	pathogenic	-0.661	Destabilizing	0.824	D	0.668	prob.neutral	None	None	None	None	N
F/R	0.7906	likely_pathogenic	0.7864	pathogenic	-0.022	Destabilizing	0.824	D	0.665	prob.neutral	None	None	None	None	N
F/S	0.3946	ambiguous	0.4147	ambiguous	-1.474	Destabilizing	0.013	N	0.45	neutral	N	0.474418593	None	None	N
F/T	0.6013	likely_pathogenic	0.6054	pathogenic	-1.333	Destabilizing	0.4	N	0.563	neutral	None	None	None	None	N
F/V	0.3534	ambiguous	0.3482	ambiguous	-1.337	Destabilizing	0.172	N	0.531	neutral	N	0.467431119	None	None	N
F/W	0.5132	ambiguous	0.4988	ambiguous	-0.27	Destabilizing	0.905	D	0.459	neutral	None	None	None	None	N
F/Y	0.1125	likely_benign	0.1191	benign	-0.423	Destabilizing	0.006	N	0.135	neutral	N	0.396208526	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.