TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26632	80119;80120;80121	chr2:178566238;178566237;178566236	chr2:179430965;179430964;179430963
N2AB	24991	75196;75197;75198	chr2:178566238;178566237;178566236	chr2:179430965;179430964;179430963
N2A	24064	72415;72416;72417	chr2:178566238;178566237;178566236	chr2:179430965;179430964;179430963
N2B	17567	52924;52925;52926	chr2:178566238;178566237;178566236	chr2:179430965;179430964;179430963
Novex-1	17692	53299;53300;53301	chr2:178566238;178566237;178566236	chr2:179430965;179430964;179430963
Novex-2	17759	53500;53501;53502	chr2:178566238;178566237;178566236	chr2:179430965;179430964;179430963
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-138
• Domain position: 39
• Structural Position: 56
• Q(SASA): 0.5858
• 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	None	None	0.722	D	0.511	0.372	0.411265580357	gnomAD-4.0.0	1.20035E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.31253E-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
E/A	0.1034	likely_benign	0.0927	benign	-0.051	Destabilizing	0.034	N	0.324	neutral	D	0.527864368	None	None	N
E/C	0.6071	likely_pathogenic	0.5391	ambiguous	-0.348	Destabilizing	0.996	D	0.678	prob.neutral	None	None	None	None	N
E/D	0.0748	likely_benign	0.0696	benign	-0.347	Destabilizing	0.003	N	0.243	neutral	N	0.492250285	None	None	N
E/F	0.5062	ambiguous	0.4282	ambiguous	0.003	Stabilizing	0.987	D	0.647	neutral	None	None	None	None	N
E/G	0.1213	likely_benign	0.1065	benign	-0.174	Destabilizing	0.722	D	0.513	neutral	N	0.498622932	None	None	N
E/H	0.2933	likely_benign	0.2555	benign	0.692	Stabilizing	0.996	D	0.547	neutral	None	None	None	None	N
E/I	0.1525	likely_benign	0.1372	benign	0.221	Stabilizing	0.961	D	0.652	neutral	None	None	None	None	N
E/K	0.115	likely_benign	0.1058	benign	0.377	Stabilizing	0.722	D	0.511	neutral	D	0.522783835	None	None	N
E/L	0.227	likely_benign	0.1914	benign	0.221	Stabilizing	0.923	D	0.567	neutral	None	None	None	None	N
E/M	0.2654	likely_benign	0.2408	benign	-0.09	Destabilizing	0.996	D	0.632	neutral	None	None	None	None	N
E/N	0.122	likely_benign	0.1052	benign	0.016	Stabilizing	0.858	D	0.497	neutral	None	None	None	None	N
E/P	0.3058	likely_benign	0.2639	benign	0.148	Stabilizing	0.961	D	0.563	neutral	None	None	None	None	N
E/Q	0.1121	likely_benign	0.1047	benign	0.046	Stabilizing	0.901	D	0.489	neutral	N	0.512876273	None	None	N
E/R	0.2049	likely_benign	0.1818	benign	0.682	Stabilizing	0.961	D	0.545	neutral	None	None	None	None	N
E/S	0.1134	likely_benign	0.1011	benign	-0.104	Destabilizing	0.633	D	0.49	neutral	None	None	None	None	N
E/T	0.1195	likely_benign	0.1093	benign	0.013	Stabilizing	0.775	D	0.506	neutral	None	None	None	None	N
E/V	0.1102	likely_benign	0.1005	benign	0.148	Stabilizing	0.901	D	0.501	neutral	N	0.481689361	None	None	N
E/W	0.791	likely_pathogenic	0.7214	pathogenic	0.08	Stabilizing	0.996	D	0.702	prob.neutral	None	None	None	None	N
E/Y	0.3773	ambiguous	0.3176	benign	0.233	Stabilizing	0.987	D	0.624	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.