TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9541	28846;28847;28848	chr2:178709698;178709697;178709696	chr2:179574425;179574424;179574423
N2AB	9224	27895;27896;27897	chr2:178709698;178709697;178709696	chr2:179574425;179574424;179574423
N2A	8297	25114;25115;25116	chr2:178709698;178709697;178709696	chr2:179574425;179574424;179574423
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: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-81
• Domain position: 49
• Structural Position: 122
• Q(SASA): 0.5054
• 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
E/K	rs2076382239	None	0.005	None	0.117	0.247	0.303453137403	gnomAD-4.0.0	1.5911E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43275E-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
E/A	0.2085	likely_benign	0.1809	benign	-0.62	Destabilizing	0.801	D	0.408	neutral	None	None	None	None	N
E/C	0.8709	likely_pathogenic	0.8445	pathogenic	-0.217	Destabilizing	0.998	D	0.615	neutral	None	None	None	None	N
E/D	0.1054	likely_benign	0.095	benign	-1.018	Destabilizing	0.005	N	0.109	neutral	None	None	None	None	N
E/F	0.7359	likely_pathogenic	0.6899	pathogenic	-0.499	Destabilizing	0.991	D	0.58	neutral	None	None	None	None	N
E/G	0.2851	likely_benign	0.222	benign	-0.931	Destabilizing	0.801	D	0.473	neutral	None	None	None	None	N
E/H	0.4419	ambiguous	0.396	ambiguous	-0.862	Destabilizing	0.991	D	0.431	neutral	None	None	None	None	N
E/I	0.3362	likely_benign	0.306	benign	0.204	Stabilizing	0.974	D	0.577	neutral	None	None	None	None	N
E/K	0.2014	likely_benign	0.163	benign	-0.262	Destabilizing	0.005	N	0.117	neutral	None	None	None	None	N
E/L	0.4176	ambiguous	0.3769	ambiguous	0.204	Stabilizing	0.949	D	0.52	neutral	None	None	None	None	N
E/M	0.4706	ambiguous	0.4248	ambiguous	0.611	Stabilizing	0.998	D	0.57	neutral	None	None	None	None	N
E/N	0.2178	likely_benign	0.1903	benign	-0.592	Destabilizing	0.842	D	0.384	neutral	None	None	None	None	N
E/P	0.9499	likely_pathogenic	0.9104	pathogenic	-0.049	Destabilizing	0.974	D	0.481	neutral	None	None	None	None	N
E/Q	0.1656	likely_benign	0.1483	benign	-0.516	Destabilizing	0.801	D	0.406	neutral	None	None	None	None	N
E/R	0.3413	ambiguous	0.2822	benign	-0.203	Destabilizing	0.728	D	0.384	neutral	None	None	None	None	N
E/S	0.2088	likely_benign	0.1827	benign	-0.859	Destabilizing	0.842	D	0.333	neutral	None	None	None	None	N
E/T	0.2269	likely_benign	0.2095	benign	-0.602	Destabilizing	0.842	D	0.46	neutral	None	None	None	None	N
E/V	0.227	likely_benign	0.2029	benign	-0.049	Destabilizing	0.966	D	0.513	neutral	None	None	None	None	N
E/W	0.9219	likely_pathogenic	0.886	pathogenic	-0.384	Destabilizing	0.998	D	0.635	neutral	None	None	None	None	N
E/Y	0.6415	likely_pathogenic	0.5719	pathogenic	-0.261	Destabilizing	0.991	D	0.581	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.