TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17910	53953;53954;53955	chr2:178605567;178605566;178605565	chr2:179470294;179470293;179470292
N2AB	16269	49030;49031;49032	chr2:178605567;178605566;178605565	chr2:179470294;179470293;179470292
N2A	15342	46249;46250;46251	chr2:178605567;178605566;178605565	chr2:179470294;179470293;179470292
N2B	8845	26758;26759;26760	chr2:178605567;178605566;178605565	chr2:179470294;179470293;179470292
Novex-1	8970	27133;27134;27135	chr2:178605567;178605566;178605565	chr2:179470294;179470293;179470292
Novex-2	9037	27334;27335;27336	chr2:178605567;178605566;178605565	chr2:179470294;179470293;179470292
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: Fn3-18
• Domain position: 49
• Structural Position: 66
• Q(SASA): 0.5313
• 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/Q	rs966575531	None	0.294	N	0.246	0.186	0.229264304666	gnomAD-4.0.0	2.10121E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.83163E-06	0	1.71697E-05

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	0.1998	likely_benign	0.2192	benign	-0.728	Destabilizing	0.698	D	0.555	neutral	N	0.483328865	None	None	N
E/C	0.7172	likely_pathogenic	0.7464	pathogenic	-0.472	Destabilizing	0.998	D	0.695	prob.neutral	None	None	None	None	N
E/D	0.1567	likely_benign	0.1759	benign	-0.863	Destabilizing	0.014	N	0.216	neutral	N	0.456990413	None	None	N
E/F	0.6644	likely_pathogenic	0.6971	pathogenic	-0.079	Destabilizing	0.956	D	0.641	neutral	None	None	None	None	N
E/G	0.3285	likely_benign	0.352	ambiguous	-1.057	Destabilizing	0.904	D	0.517	neutral	N	0.520193742	None	None	N
E/H	0.3689	ambiguous	0.3909	ambiguous	-0.043	Destabilizing	0.994	D	0.573	neutral	None	None	None	None	N
E/I	0.196	likely_benign	0.2005	benign	0.16	Stabilizing	0.915	D	0.581	neutral	None	None	None	None	N
E/K	0.2052	likely_benign	0.2028	benign	-0.339	Destabilizing	0.698	D	0.576	neutral	N	0.461222797	None	None	N
E/L	0.2954	likely_benign	0.3155	benign	0.16	Stabilizing	0.754	D	0.534	neutral	None	None	None	None	N
E/M	0.3729	ambiguous	0.3982	ambiguous	0.355	Stabilizing	0.994	D	0.627	neutral	None	None	None	None	N
E/N	0.3166	likely_benign	0.3397	benign	-0.925	Destabilizing	0.956	D	0.526	neutral	None	None	None	None	N
E/P	0.9192	likely_pathogenic	0.9191	pathogenic	-0.115	Destabilizing	0.993	D	0.588	neutral	None	None	None	None	N
E/Q	0.1188	likely_benign	0.1217	benign	-0.806	Destabilizing	0.294	N	0.246	neutral	N	0.429689168	None	None	N
E/R	0.2989	likely_benign	0.3048	benign	0.072	Stabilizing	0.956	D	0.555	neutral	None	None	None	None	N
E/S	0.2187	likely_benign	0.2306	benign	-1.154	Destabilizing	0.86	D	0.543	neutral	None	None	None	None	N
E/T	0.1815	likely_benign	0.1929	benign	-0.879	Destabilizing	0.86	D	0.523	neutral	None	None	None	None	N
E/V	0.1279	likely_benign	0.1309	benign	-0.115	Destabilizing	0.032	N	0.351	neutral	N	0.447600138	None	None	N
E/W	0.8703	likely_pathogenic	0.8729	pathogenic	0.221	Stabilizing	0.998	D	0.703	prob.neutral	None	None	None	None	N
E/Y	0.5824	likely_pathogenic	0.599	pathogenic	0.187	Stabilizing	0.978	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.