TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2939	9040;9041;9042	chr2:178769766;178769765;178769764	chr2:179634493;179634492;179634491
N2AB	2939	9040;9041;9042	chr2:178769766;178769765;178769764	chr2:179634493;179634492;179634491
N2A	2939	9040;9041;9042	chr2:178769766;178769765;178769764	chr2:179634493;179634492;179634491
N2B	2893	8902;8903;8904	chr2:178769766;178769765;178769764	chr2:179634493;179634492;179634491
Novex-1	2893	8902;8903;8904	chr2:178769766;178769765;178769764	chr2:179634493;179634492;179634491
Novex-2	2893	8902;8903;8904	chr2:178769766;178769765;178769764	chr2:179634493;179634492;179634491
Novex-3	2939	9040;9041;9042	chr2:178769766;178769765;178769764	chr2:179634493;179634492;179634491

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Ig-19
• Domain position: 58
• Structural Position: 139
• Q(SASA): 0.1596
• 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
I/T	None	None	0.285	N	0.523	0.249	0.560681312399	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	6.33473E-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
I/A	0.688	likely_pathogenic	0.5591	ambiguous	-2.364	Highly Destabilizing	0.209	N	0.441	neutral	None	None	None	None	N
I/C	0.7638	likely_pathogenic	0.7124	pathogenic	-1.598	Destabilizing	0.991	D	0.495	neutral	None	None	None	None	N
I/D	0.8937	likely_pathogenic	0.8503	pathogenic	-2.29	Highly Destabilizing	0.39	N	0.533	neutral	None	None	None	None	N
I/E	0.8023	likely_pathogenic	0.7265	pathogenic	-2.193	Highly Destabilizing	0.561	D	0.515	neutral	None	None	None	None	N
I/F	0.2662	likely_benign	0.2146	benign	-1.498	Destabilizing	0.772	D	0.484	neutral	N	0.50712909	None	None	N
I/G	0.8976	likely_pathogenic	0.8399	pathogenic	-2.796	Highly Destabilizing	0.39	N	0.511	neutral	None	None	None	None	N
I/H	0.5523	ambiguous	0.5098	ambiguous	-2.028	Highly Destabilizing	0.901	D	0.535	neutral	None	None	None	None	N
I/K	0.5946	likely_pathogenic	0.4998	ambiguous	-1.791	Destabilizing	0.007	N	0.42	neutral	None	None	None	None	N
I/L	0.1592	likely_benign	0.1127	benign	-1.173	Destabilizing	0.029	N	0.326	neutral	N	0.490958679	None	None	N
I/M	0.1353	likely_benign	0.0897	benign	-0.982	Destabilizing	0.08	N	0.339	neutral	N	0.512916716	None	None	N
I/N	0.4192	ambiguous	0.3463	ambiguous	-1.775	Destabilizing	0.003	N	0.457	neutral	D	0.530081428	None	None	N
I/P	0.9927	likely_pathogenic	0.9878	pathogenic	-1.545	Destabilizing	0.965	D	0.569	neutral	None	None	None	None	N
I/Q	0.5799	likely_pathogenic	0.4853	ambiguous	-1.859	Destabilizing	0.818	D	0.574	neutral	None	None	None	None	N
I/R	0.4887	ambiguous	0.407	ambiguous	-1.227	Destabilizing	0.39	N	0.532	neutral	None	None	None	None	N
I/S	0.5722	likely_pathogenic	0.4591	ambiguous	-2.451	Highly Destabilizing	0.326	N	0.518	neutral	N	0.507638781	None	None	N
I/T	0.4464	ambiguous	0.3271	benign	-2.234	Highly Destabilizing	0.285	N	0.523	neutral	N	0.439923164	None	None	N
I/V	0.1162	likely_benign	0.0804	benign	-1.545	Destabilizing	0.001	N	0.185	neutral	N	0.47341656	None	None	N
I/W	0.787	likely_pathogenic	0.7746	pathogenic	-1.711	Destabilizing	0.991	D	0.573	neutral	None	None	None	None	N
I/Y	0.5445	ambiguous	0.5065	ambiguous	-1.502	Destabilizing	0.901	D	0.525	neutral	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.