TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8136	24631;24632;24633	chr2:178718794;178718793;178718792	chr2:179583521;179583520;179583519
N2AB	7819	23680;23681;23682	chr2:178718794;178718793;178718792	chr2:179583521;179583520;179583519
N2A	6892	20899;20900;20901	chr2:178718794;178718793;178718792	chr2:179583521;179583520;179583519
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: GAG
• RefSeq wild type template codon: CTC
• Domain: Ig-66
• Domain position: 59
• Structural Position: 139
• Q(SASA): 0.2345
• 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/G	None	None	0.722	D	0.594	0.488	0.561714622075	gnomAD-4.0.0	1.59127E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85834E-06	0	0
E/Q	None	None	0.075	N	0.41	0.182	0.272639205421	gnomAD-4.0.0	3.60097E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.9375E-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	0.2097	likely_benign	0.2111	benign	-1.159	Destabilizing	0.722	D	0.547	neutral	N	0.496403979	None	None	N
E/C	0.8618	likely_pathogenic	0.8563	pathogenic	-0.689	Destabilizing	0.996	D	0.732	prob.delet.	None	None	None	None	N
E/D	0.2789	likely_benign	0.299	benign	-1.361	Destabilizing	0.003	N	0.251	neutral	N	0.50738189	None	None	N
E/F	0.7121	likely_pathogenic	0.7181	pathogenic	-0.819	Destabilizing	0.961	D	0.725	prob.delet.	None	None	None	None	N
E/G	0.2976	likely_benign	0.301	benign	-1.555	Destabilizing	0.722	D	0.594	neutral	D	0.522523631	None	None	N
E/H	0.3687	ambiguous	0.3804	ambiguous	-1.126	Destabilizing	0.961	D	0.575	neutral	None	None	None	None	N
E/I	0.3591	ambiguous	0.3684	ambiguous	-0.056	Destabilizing	0.096	N	0.514	neutral	None	None	None	None	N
E/K	0.1597	likely_benign	0.1728	benign	-1.023	Destabilizing	0.565	D	0.543	neutral	N	0.489162277	None	None	N
E/L	0.3776	ambiguous	0.3906	ambiguous	-0.056	Destabilizing	0.633	D	0.611	neutral	None	None	None	None	N
E/M	0.437	ambiguous	0.4416	ambiguous	0.574	Stabilizing	0.989	D	0.682	prob.neutral	None	None	None	None	N
E/N	0.3658	ambiguous	0.3902	ambiguous	-1.364	Destabilizing	0.858	D	0.545	neutral	None	None	None	None	N
E/P	0.9712	likely_pathogenic	0.9694	pathogenic	-0.404	Destabilizing	0.961	D	0.635	neutral	None	None	None	None	N
E/Q	0.1039	likely_benign	0.1034	benign	-1.19	Destabilizing	0.075	N	0.41	neutral	N	0.4841623	None	None	N
E/R	0.2335	likely_benign	0.243	benign	-0.868	Destabilizing	0.858	D	0.558	neutral	None	None	None	None	N
E/S	0.2541	likely_benign	0.2558	benign	-1.879	Destabilizing	0.775	D	0.514	neutral	None	None	None	None	N
E/T	0.242	likely_benign	0.2461	benign	-1.53	Destabilizing	0.775	D	0.569	neutral	None	None	None	None	N
E/V	0.2122	likely_benign	0.2165	benign	-0.404	Destabilizing	0.565	D	0.577	neutral	N	0.497021386	None	None	N
E/W	0.8833	likely_pathogenic	0.8844	pathogenic	-0.695	Destabilizing	0.996	D	0.711	prob.delet.	None	None	None	None	N
E/Y	0.6165	likely_pathogenic	0.6312	pathogenic	-0.578	Destabilizing	0.987	D	0.686	prob.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.