TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25159	75700;75701;75702	chr2:178570657;178570656;178570655	chr2:179435384;179435383;179435382
N2AB	23518	70777;70778;70779	chr2:178570657;178570656;178570655	chr2:179435384;179435383;179435382
N2A	22591	67996;67997;67998	chr2:178570657;178570656;178570655	chr2:179435384;179435383;179435382
N2B	16094	48505;48506;48507	chr2:178570657;178570656;178570655	chr2:179435384;179435383;179435382
Novex-1	16219	48880;48881;48882	chr2:178570657;178570656;178570655	chr2:179435384;179435383;179435382
Novex-2	16286	49081;49082;49083	chr2:178570657;178570656;178570655	chr2:179435384;179435383;179435382
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-134
• Domain position: 49
• Structural Position: 122
• Q(SASA): 0.3549
• 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/G	None	None	0.722	N	0.462	0.311	0.481246930725	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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	0.2337	likely_benign	0.264	benign	-0.869	Destabilizing	0.565	D	0.433	neutral	N	0.492542865	None	None	N
E/C	0.8384	likely_pathogenic	0.8734	pathogenic	-0.259	Destabilizing	0.996	D	0.684	prob.neutral	None	None	None	None	N
E/D	0.1643	likely_benign	0.1577	benign	-0.94	Destabilizing	0.003	N	0.129	neutral	D	0.523477269	None	None	N
E/F	0.7666	likely_pathogenic	0.8148	pathogenic	-0.79	Destabilizing	0.987	D	0.66	neutral	None	None	None	None	N
E/G	0.3195	likely_benign	0.3609	ambiguous	-1.157	Destabilizing	0.722	D	0.462	neutral	N	0.494063802	None	None	N
E/H	0.492	ambiguous	0.5483	ambiguous	-1.069	Destabilizing	0.989	D	0.475	neutral	None	None	None	None	N
E/I	0.3674	ambiguous	0.4287	ambiguous	-0.106	Destabilizing	0.961	D	0.671	neutral	None	None	None	None	N
E/K	0.3148	likely_benign	0.3801	ambiguous	-0.247	Destabilizing	0.008	N	0.263	neutral	N	0.506947591	None	None	N
E/L	0.4551	ambiguous	0.524	ambiguous	-0.106	Destabilizing	0.923	D	0.599	neutral	None	None	None	None	N
E/M	0.4763	ambiguous	0.5415	ambiguous	0.406	Stabilizing	0.996	D	0.635	neutral	None	None	None	None	N
E/N	0.3255	likely_benign	0.3576	ambiguous	-0.589	Destabilizing	0.633	D	0.416	neutral	None	None	None	None	N
E/P	0.9775	likely_pathogenic	0.9851	pathogenic	-0.34	Destabilizing	0.961	D	0.569	neutral	None	None	None	None	N
E/Q	0.1675	likely_benign	0.1949	benign	-0.541	Destabilizing	0.722	D	0.423	neutral	N	0.518396736	None	None	N
E/R	0.4453	ambiguous	0.5186	ambiguous	-0.191	Destabilizing	0.858	D	0.439	neutral	None	None	None	None	N
E/S	0.2705	likely_benign	0.3019	benign	-0.862	Destabilizing	0.633	D	0.391	neutral	None	None	None	None	N
E/T	0.2701	likely_benign	0.2993	benign	-0.617	Destabilizing	0.923	D	0.469	neutral	None	None	None	None	N
E/V	0.227	likely_benign	0.2554	benign	-0.34	Destabilizing	0.901	D	0.555	neutral	N	0.484326885	None	None	N
E/W	0.9099	likely_pathogenic	0.9313	pathogenic	-0.622	Destabilizing	0.996	D	0.682	prob.neutral	None	None	None	None	N
E/Y	0.6724	likely_pathogenic	0.7309	pathogenic	-0.535	Destabilizing	0.987	D	0.641	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.