TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9178	27757;27758;27759	chr2:178712390;178712389;178712388	chr2:179577117;179577116;179577115
N2AB	8861	26806;26807;26808	chr2:178712390;178712389;178712388	chr2:179577117;179577116;179577115
N2A	7934	24025;24026;24027	chr2:178712390;178712389;178712388	chr2:179577117;179577116;179577115
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: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Ig-77
• Domain position: 67
• Structural Position: 149
• Q(SASA): 0.139
• 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
D/G	rs747327863	-0.475	0.826	D	0.677	0.772	0.596650592983	gnomAD-2.1.1	8.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.77E-05	0
D/G	rs747327863	-0.475	0.826	D	0.677	0.772	0.596650592983	gnomAD-4.0.0	6.36472E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.14318E-05	0	0
D/V	None	None	0.92	D	0.766	0.782	0.782820974753	gnomAD-4.0.0	1.59118E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85796E-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
D/A	0.8767	likely_pathogenic	0.821	pathogenic	-0.14	Destabilizing	0.061	N	0.476	neutral	D	0.573062271	None	None	N
D/C	0.9759	likely_pathogenic	0.9673	pathogenic	0.025	Stabilizing	0.999	D	0.826	deleterious	None	None	None	None	N
D/E	0.7999	likely_pathogenic	0.7313	pathogenic	-0.688	Destabilizing	0.826	D	0.614	neutral	D	0.601104192	None	None	N
D/F	0.9745	likely_pathogenic	0.9586	pathogenic	0.511	Stabilizing	0.997	D	0.83	deleterious	None	None	None	None	N
D/G	0.9158	likely_pathogenic	0.8701	pathogenic	-0.575	Destabilizing	0.826	D	0.677	prob.neutral	D	0.639663166	None	None	N
D/H	0.9066	likely_pathogenic	0.8556	pathogenic	0.19	Stabilizing	0.999	D	0.785	deleterious	D	0.593199875	None	None	N
D/I	0.9667	likely_pathogenic	0.9428	pathogenic	1.031	Stabilizing	0.982	D	0.815	deleterious	None	None	None	None	N
D/K	0.9834	likely_pathogenic	0.9704	pathogenic	-0.012	Destabilizing	0.939	D	0.711	prob.delet.	None	None	None	None	N
D/L	0.9671	likely_pathogenic	0.9427	pathogenic	1.031	Stabilizing	0.939	D	0.765	deleterious	None	None	None	None	N
D/M	0.9733	likely_pathogenic	0.9586	pathogenic	1.482	Stabilizing	0.999	D	0.827	deleterious	None	None	None	None	N
D/N	0.7011	likely_pathogenic	0.6128	pathogenic	-0.805	Destabilizing	0.92	D	0.656	neutral	D	0.596289455	None	None	N
D/P	0.9982	likely_pathogenic	0.9964	pathogenic	0.669	Stabilizing	0.991	D	0.785	deleterious	None	None	None	None	N
D/Q	0.9694	likely_pathogenic	0.9505	pathogenic	-0.531	Destabilizing	0.991	D	0.721	prob.delet.	None	None	None	None	N
D/R	0.9891	likely_pathogenic	0.9802	pathogenic	0.083	Stabilizing	0.991	D	0.806	deleterious	None	None	None	None	N
D/S	0.8684	likely_pathogenic	0.8033	pathogenic	-1.059	Destabilizing	0.373	N	0.359	neutral	None	None	None	None	N
D/T	0.9467	likely_pathogenic	0.9115	pathogenic	-0.663	Destabilizing	0.17	N	0.492	neutral	None	None	None	None	N
D/V	0.9139	likely_pathogenic	0.8674	pathogenic	0.669	Stabilizing	0.92	D	0.766	deleterious	D	0.6563183	None	None	N
D/W	0.9953	likely_pathogenic	0.9924	pathogenic	0.68	Stabilizing	0.999	D	0.826	deleterious	None	None	None	None	N
D/Y	0.842	likely_pathogenic	0.7676	pathogenic	0.795	Stabilizing	0.996	D	0.819	deleterious	D	0.630578384	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.