TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9436	28531;28532;28533	chr2:178710791;178710790;178710789	chr2:179575518;179575517;179575516
N2AB	9119	27580;27581;27582	chr2:178710791;178710790;178710789	chr2:179575518;179575517;179575516
N2A	8192	24799;24800;24801	chr2:178710791;178710790;178710789	chr2:179575518;179575517;179575516
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-80
• Domain position: 40
• Structural Position: 56
• Q(SASA): 0.4884
• 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/D	rs906433178	None	0.003	None	0.145	0.099	0.270447802918	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	0	1.30907E-04	0	0	0	None	0	0	0	0	0
E/D	rs906433178	None	0.003	None	0.145	0.099	0.270447802918	gnomAD-4.0.0	1.85895E-06	None	None	None	None	N	None	0	5.0005E-05	None	0	0	None	0	0	0	0	0
E/Q	None	None	0.034	None	0.249	0.127	0.251639045875	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	0.213	likely_benign	0.2701	benign	-0.334	Destabilizing	0.565	D	0.494	neutral	None	None	None	None	N
E/C	0.936	likely_pathogenic	0.9669	pathogenic	-0.114	Destabilizing	0.996	D	0.725	prob.delet.	None	None	None	None	N
E/D	0.1305	likely_benign	0.1686	benign	-0.442	Destabilizing	0.003	N	0.145	neutral	None	None	None	None	N
E/F	0.8026	likely_pathogenic	0.8925	pathogenic	-0.169	Destabilizing	0.987	D	0.669	neutral	None	None	None	None	N
E/G	0.2666	likely_benign	0.3685	ambiguous	-0.532	Destabilizing	0.722	D	0.541	neutral	None	None	None	None	N
E/H	0.6227	likely_pathogenic	0.7765	pathogenic	0.138	Stabilizing	0.961	D	0.504	neutral	None	None	None	None	N
E/I	0.4384	ambiguous	0.5342	ambiguous	0.154	Stabilizing	0.961	D	0.669	neutral	None	None	None	None	N
E/K	0.2858	likely_benign	0.355	ambiguous	0.361	Stabilizing	0.565	D	0.479	neutral	None	None	None	None	N
E/L	0.4716	ambiguous	0.5638	ambiguous	0.154	Stabilizing	0.923	D	0.579	neutral	None	None	None	None	N
E/M	0.5532	ambiguous	0.6582	pathogenic	0.144	Stabilizing	0.989	D	0.65	neutral	None	None	None	None	N
E/N	0.3145	likely_benign	0.4405	ambiguous	-0.059	Destabilizing	0.775	D	0.469	neutral	None	None	None	None	N
E/P	0.3846	ambiguous	0.4618	ambiguous	0.012	Stabilizing	0.961	D	0.552	neutral	None	None	None	None	N
E/Q	0.2094	likely_benign	0.2932	benign	-0.016	Destabilizing	0.034	N	0.249	neutral	None	None	None	None	N
E/R	0.4332	ambiguous	0.5615	ambiguous	0.596	Stabilizing	0.858	D	0.462	neutral	None	None	None	None	N
E/S	0.3174	likely_benign	0.443	ambiguous	-0.178	Destabilizing	0.633	D	0.443	neutral	None	None	None	None	N
E/T	0.325	likely_benign	0.4306	ambiguous	-0.013	Destabilizing	0.775	D	0.535	neutral	None	None	None	None	N
E/V	0.2654	likely_benign	0.3305	benign	0.012	Stabilizing	0.901	D	0.566	neutral	None	None	None	None	N
E/W	0.9265	likely_pathogenic	0.9666	pathogenic	-0.011	Destabilizing	0.996	D	0.731	prob.delet.	None	None	None	None	N
E/Y	0.7042	likely_pathogenic	0.834	pathogenic	0.08	Stabilizing	0.961	D	0.654	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.