TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32127	96604;96605;96606	chr2:178543594;178543593;178543592	chr2:179408321;179408320;179408319
N2AB	30486	91681;91682;91683	chr2:178543594;178543593;178543592	chr2:179408321;179408320;179408319
N2A	29559	88900;88901;88902	chr2:178543594;178543593;178543592	chr2:179408321;179408320;179408319
N2B	23062	69409;69410;69411	chr2:178543594;178543593;178543592	chr2:179408321;179408320;179408319
Novex-1	23187	69784;69785;69786	chr2:178543594;178543593;178543592	chr2:179408321;179408320;179408319
Novex-2	23254	69985;69986;69987	chr2:178543594;178543593;178543592	chr2:179408321;179408320;179408319
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: Fn3-122
• Domain position: 23
• Structural Position: 25
• Q(SASA): 0.5388
• 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/A	None	None	0.896	N	0.637	0.362	0.305086939656	gnomAD-4.0.0	2.7501E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.69889E-06	0	1.6581E-05
E/Q	None	None	0.946	N	0.585	0.187	0.242244723065	gnomAD-4.0.0	1.60953E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86E-06	0	0
E/V	None	None	0.984	N	0.703	0.453	0.470484629704	gnomAD-4.0.0	6.87524E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99628E-07	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	0.1744	likely_benign	0.1604	benign	-0.864	Destabilizing	0.896	D	0.637	neutral	N	0.458838639	None	None	N
E/C	0.8018	likely_pathogenic	0.7949	pathogenic	-0.447	Destabilizing	0.999	D	0.785	deleterious	None	None	None	None	N
E/D	0.0664	likely_benign	0.0654	benign	-0.975	Destabilizing	0.004	N	0.172	neutral	N	0.424301991	None	None	N
E/F	0.8441	likely_pathogenic	0.8246	pathogenic	-0.46	Destabilizing	0.996	D	0.767	deleterious	None	None	None	None	N
E/G	0.1618	likely_benign	0.1369	benign	-1.186	Destabilizing	0.896	D	0.643	neutral	N	0.482696934	None	None	N
E/H	0.5404	ambiguous	0.4951	ambiguous	-0.654	Destabilizing	0.996	D	0.623	neutral	None	None	None	None	N
E/I	0.5208	ambiguous	0.4903	ambiguous	None	Stabilizing	0.988	D	0.77	deleterious	None	None	None	None	N
E/K	0.3022	likely_benign	0.2502	benign	-0.559	Destabilizing	0.896	D	0.573	neutral	N	0.441578243	None	None	N
E/L	0.5082	ambiguous	0.4825	ambiguous	None	Stabilizing	0.988	D	0.735	prob.delet.	None	None	None	None	N
E/M	0.5343	ambiguous	0.5102	ambiguous	0.376	Stabilizing	0.999	D	0.759	deleterious	None	None	None	None	N
E/N	0.1676	likely_benign	0.1534	benign	-0.937	Destabilizing	0.851	D	0.581	neutral	None	None	None	None	N
E/P	0.616	likely_pathogenic	0.5996	pathogenic	-0.267	Destabilizing	0.988	D	0.711	prob.delet.	None	None	None	None	N
E/Q	0.1866	likely_benign	0.1687	benign	-0.848	Destabilizing	0.946	D	0.585	neutral	N	0.463359025	None	None	N
E/R	0.4524	ambiguous	0.3877	ambiguous	-0.273	Destabilizing	0.988	D	0.625	neutral	None	None	None	None	N
E/S	0.1845	likely_benign	0.1655	benign	-1.214	Destabilizing	0.919	D	0.565	neutral	None	None	None	None	N
E/T	0.2521	likely_benign	0.2367	benign	-0.957	Destabilizing	0.919	D	0.678	prob.neutral	None	None	None	None	N
E/V	0.3111	likely_benign	0.2897	benign	-0.267	Destabilizing	0.984	D	0.703	prob.neutral	N	0.495183442	None	None	N
E/W	0.9268	likely_pathogenic	0.9132	pathogenic	-0.231	Destabilizing	0.999	D	0.763	deleterious	None	None	None	None	N
E/Y	0.6946	likely_pathogenic	0.6516	pathogenic	-0.224	Destabilizing	0.996	D	0.773	deleterious	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.