TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22031	66316;66317;66318	chr2:178582365;178582364;178582363	chr2:179447092;179447091;179447090
N2AB	20390	61393;61394;61395	chr2:178582365;178582364;178582363	chr2:179447092;179447091;179447090
N2A	19463	58612;58613;58614	chr2:178582365;178582364;178582363	chr2:179447092;179447091;179447090
N2B	12966	39121;39122;39123	chr2:178582365;178582364;178582363	chr2:179447092;179447091;179447090
Novex-1	13091	39496;39497;39498	chr2:178582365;178582364;178582363	chr2:179447092;179447091;179447090
Novex-2	13158	39697;39698;39699	chr2:178582365;178582364;178582363	chr2:179447092;179447091;179447090
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: C
• RefSeq wild type transcript codon: TGT
• RefSeq wild type template codon: ACA
• Domain: Fn3-47
• Domain position: 76
• Structural Position: 109
• Q(SASA): 0.0958
• 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
C/S	rs1437140291	-2.078	0.002	N	0.388	0.261	0.424908009808	gnomAD-2.1.1	3.19E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	2.87853E-04	0	0
C/S	rs1437140291	-2.078	0.002	N	0.388	0.261	0.424908009808	gnomAD-4.0.0	1.5977E-06	None	None	None	None	N	None	0	0	None	0	0	None	1.88523E-05	0	0	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
C/A	0.3804	ambiguous	0.357	ambiguous	-1.635	Destabilizing	0.002	N	0.193	neutral	None	None	None	None	N
C/D	0.9159	likely_pathogenic	0.9088	pathogenic	-1.711	Destabilizing	0.561	D	0.719	prob.delet.	None	None	None	None	N
C/E	0.895	likely_pathogenic	0.8844	pathogenic	-1.494	Destabilizing	0.561	D	0.727	prob.delet.	None	None	None	None	N
C/F	0.2527	likely_benign	0.2523	benign	-1.019	Destabilizing	0.873	D	0.728	prob.delet.	N	0.385762246	None	None	N
C/G	0.3189	likely_benign	0.2797	benign	-1.972	Destabilizing	0.166	N	0.729	prob.delet.	N	0.460182647	None	None	N
C/H	0.4558	ambiguous	0.4573	ambiguous	-2.285	Highly Destabilizing	0.901	D	0.733	prob.delet.	None	None	None	None	N
C/I	0.6309	likely_pathogenic	0.6351	pathogenic	-0.732	Destabilizing	0.561	D	0.697	prob.neutral	None	None	None	None	N
C/K	0.7737	likely_pathogenic	0.7832	pathogenic	-1.404	Destabilizing	0.209	N	0.711	prob.delet.	None	None	None	None	N
C/L	0.4984	ambiguous	0.4792	ambiguous	-0.732	Destabilizing	0.345	N	0.683	prob.neutral	None	None	None	None	N
C/M	0.5401	ambiguous	0.5308	ambiguous	-0.083	Destabilizing	0.965	D	0.697	prob.neutral	None	None	None	None	N
C/N	0.6481	likely_pathogenic	0.6201	pathogenic	-1.889	Destabilizing	0.561	D	0.723	prob.delet.	None	None	None	None	N
C/P	0.9979	likely_pathogenic	0.9975	pathogenic	-1.01	Destabilizing	0.722	D	0.735	prob.delet.	None	None	None	None	N
C/Q	0.5074	ambiguous	0.5208	ambiguous	-1.459	Destabilizing	0.561	D	0.737	prob.delet.	None	None	None	None	N
C/R	0.3577	ambiguous	0.3711	ambiguous	-1.737	Destabilizing	0.003	N	0.601	neutral	N	0.311128414	None	None	N
C/S	0.211	likely_benign	0.203	benign	-2.175	Highly Destabilizing	0.002	N	0.388	neutral	N	0.316190304	None	None	N
C/T	0.4266	ambiguous	0.4031	ambiguous	-1.789	Destabilizing	0.209	N	0.681	prob.neutral	None	None	None	None	N
C/V	0.5	ambiguous	0.5116	ambiguous	-1.01	Destabilizing	0.209	N	0.681	prob.neutral	None	None	None	None	N
C/W	0.6018	likely_pathogenic	0.6134	pathogenic	-1.475	Destabilizing	0.987	D	0.707	prob.neutral	N	0.471573076	None	None	N
C/Y	0.3687	ambiguous	0.3691	ambiguous	-1.251	Destabilizing	0.954	D	0.717	prob.delet.	N	0.396381884	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.