TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28373	85342;85343;85344	chr2:178561015;178561014;178561013	chr2:179425742;179425741;179425740
N2AB	26732	80419;80420;80421	chr2:178561015;178561014;178561013	chr2:179425742;179425741;179425740
N2A	25805	77638;77639;77640	chr2:178561015;178561014;178561013	chr2:179425742;179425741;179425740
N2B	19308	58147;58148;58149	chr2:178561015;178561014;178561013	chr2:179425742;179425741;179425740
Novex-1	19433	58522;58523;58524	chr2:178561015;178561014;178561013	chr2:179425742;179425741;179425740
Novex-2	19500	58723;58724;58725	chr2:178561015;178561014;178561013	chr2:179425742;179425741;179425740
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Ig-143
• Domain position: 16
• Structural Position: 25
• Q(SASA): 0.5922
• Predicted PPI site: I

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	rs770787056	-0.192	0.006	N	0.198	0.071	0.0401082797425	gnomAD-2.1.1	2.5E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	5.48E-05	0
E/D	rs770787056	-0.192	0.006	N	0.198	0.071	0.0401082797425	gnomAD-3.1.2	1.97E-05	None	None	None	None	I	None	0	0	0	0	0	None	0	0	4.41E-05	0	0
E/D	rs770787056	-0.192	0.006	N	0.198	0.071	0.0401082797425	gnomAD-4.0.0	1.7971E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.28853E-05	1.09791E-05	1.60108E-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	0.2489	likely_benign	0.2218	benign	-0.528	Destabilizing	0.698	D	0.472	neutral	N	0.477029281	None	None	I
E/C	0.9039	likely_pathogenic	0.8852	pathogenic	-0.115	Destabilizing	0.998	D	0.682	prob.neutral	None	None	None	None	I
E/D	0.1212	likely_benign	0.1025	benign	-0.558	Destabilizing	0.006	N	0.198	neutral	N	0.460038213	None	None	I
E/F	0.8828	likely_pathogenic	0.8587	pathogenic	-0.373	Destabilizing	0.978	D	0.599	neutral	None	None	None	None	I
E/G	0.2315	likely_benign	0.2038	benign	-0.755	Destabilizing	0.822	D	0.474	neutral	N	0.505599931	None	None	I
E/H	0.6038	likely_pathogenic	0.5573	ambiguous	-0.261	Destabilizing	0.998	D	0.396	neutral	None	None	None	None	I
E/I	0.7061	likely_pathogenic	0.6772	pathogenic	0.044	Stabilizing	0.956	D	0.594	neutral	None	None	None	None	I
E/K	0.2161	likely_benign	0.2008	benign	0.135	Stabilizing	0.822	D	0.443	neutral	N	0.456176321	None	None	I
E/L	0.6548	likely_pathogenic	0.6177	pathogenic	0.044	Stabilizing	0.915	D	0.519	neutral	None	None	None	None	I
E/M	0.6195	likely_pathogenic	0.5876	pathogenic	0.229	Stabilizing	0.998	D	0.559	neutral	None	None	None	None	I
E/N	0.2897	likely_benign	0.252	benign	-0.212	Destabilizing	0.86	D	0.419	neutral	None	None	None	None	I
E/P	0.9679	likely_pathogenic	0.9561	pathogenic	-0.126	Destabilizing	0.978	D	0.455	neutral	None	None	None	None	I
E/Q	0.1995	likely_benign	0.1898	benign	-0.176	Destabilizing	0.97	D	0.431	neutral	N	0.455415852	None	None	I
E/R	0.38	ambiguous	0.3519	ambiguous	0.35	Stabilizing	0.956	D	0.414	neutral	None	None	None	None	I
E/S	0.2438	likely_benign	0.2233	benign	-0.383	Destabilizing	0.754	D	0.425	neutral	None	None	None	None	I
E/T	0.319	likely_benign	0.3076	benign	-0.201	Destabilizing	0.043	N	0.32	neutral	None	None	None	None	I
E/V	0.4414	ambiguous	0.4142	ambiguous	-0.126	Destabilizing	0.89	D	0.453	neutral	N	0.48751344	None	None	I
E/W	0.9558	likely_pathogenic	0.9396	pathogenic	-0.197	Destabilizing	0.998	D	0.705	prob.neutral	None	None	None	None	I
E/Y	0.7598	likely_pathogenic	0.707	pathogenic	-0.127	Destabilizing	0.993	D	0.551	neutral	None	None	None	None	I

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.