TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6998	21217;21218;21219	chr2:178724383;178724382;178724381	chr2:179589110;179589109;179589108
N2AB	6681	20266;20267;20268	chr2:178724383;178724382;178724381	chr2:179589110;179589109;179589108
N2A	5754	17485;17486;17487	chr2:178724383;178724382;178724381	chr2:179589110;179589109;179589108
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: TTC
• RefSeq wild type template codon: AAG
• Domain: Ig-54
• Domain position: 51
• Structural Position: 127
• Q(SASA): 0.1346
• 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/I	rs2078975916	None	0.669	N	0.595	0.229	0.269558022972	gnomAD-4.0.0	4.10594E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.69879E-06	3.47834E-05	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	0.8264	likely_pathogenic	0.8454	pathogenic	-1.772	Destabilizing	0.525	D	0.633	neutral	None	None	None	None	N
F/C	0.6521	likely_pathogenic	0.6942	pathogenic	-1.237	Destabilizing	0.997	D	0.677	prob.neutral	N	0.485630331	None	None	N
F/D	0.9345	likely_pathogenic	0.9337	pathogenic	0.155	Stabilizing	0.842	D	0.713	prob.delet.	None	None	None	None	N
F/E	0.9497	likely_pathogenic	0.9493	pathogenic	0.243	Stabilizing	0.842	D	0.713	prob.delet.	None	None	None	None	N
F/G	0.9284	likely_pathogenic	0.9337	pathogenic	-2.081	Highly Destabilizing	0.007	N	0.505	neutral	None	None	None	None	N
F/H	0.7833	likely_pathogenic	0.7864	pathogenic	-0.311	Destabilizing	0.998	D	0.632	neutral	None	None	None	None	N
F/I	0.3407	ambiguous	0.3468	ambiguous	-0.869	Destabilizing	0.669	D	0.595	neutral	N	0.490730132	None	None	N
F/K	0.9511	likely_pathogenic	0.9483	pathogenic	-1.033	Destabilizing	0.842	D	0.714	prob.delet.	None	None	None	None	N
F/L	0.9055	likely_pathogenic	0.9041	pathogenic	-0.869	Destabilizing	0.012	N	0.277	neutral	N	0.471701654	None	None	N
F/M	0.6959	likely_pathogenic	0.7084	pathogenic	-0.834	Destabilizing	0.949	D	0.631	neutral	None	None	None	None	N
F/N	0.8252	likely_pathogenic	0.8156	pathogenic	-1.179	Destabilizing	0.949	D	0.719	prob.delet.	None	None	None	None	N
F/P	0.9955	likely_pathogenic	0.995	pathogenic	-1.16	Destabilizing	0.974	D	0.717	prob.delet.	None	None	None	None	N
F/Q	0.9073	likely_pathogenic	0.9082	pathogenic	-1.128	Destabilizing	0.974	D	0.715	prob.delet.	None	None	None	None	N
F/R	0.8812	likely_pathogenic	0.8793	pathogenic	-0.513	Destabilizing	0.974	D	0.723	prob.delet.	None	None	None	None	N
F/S	0.6617	likely_pathogenic	0.6805	pathogenic	-2.039	Highly Destabilizing	0.062	N	0.464	neutral	N	0.460945943	None	None	N
F/T	0.7168	likely_pathogenic	0.7264	pathogenic	-1.853	Destabilizing	0.728	D	0.671	neutral	None	None	None	None	N
F/V	0.328	likely_benign	0.3461	ambiguous	-1.16	Destabilizing	0.669	D	0.607	neutral	N	0.462060664	None	None	N
F/W	0.7485	likely_pathogenic	0.7556	pathogenic	-0.01	Destabilizing	0.998	D	0.624	neutral	None	None	None	None	N
F/Y	0.2892	likely_benign	0.2834	benign	-0.266	Destabilizing	0.961	D	0.595	neutral	N	0.48033978	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.