TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26456	79591;79592;79593	chr2:178566766;178566765;178566764	chr2:179431493;179431492;179431491
N2AB	24815	74668;74669;74670	chr2:178566766;178566765;178566764	chr2:179431493;179431492;179431491
N2A	23888	71887;71888;71889	chr2:178566766;178566765;178566764	chr2:179431493;179431492;179431491
N2B	17391	52396;52397;52398	chr2:178566766;178566765;178566764	chr2:179431493;179431492;179431491
Novex-1	17516	52771;52772;52773	chr2:178566766;178566765;178566764	chr2:179431493;179431492;179431491
Novex-2	17583	52972;52973;52974	chr2:178566766;178566765;178566764	chr2:179431493;179431492;179431491
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: Fn3-80
• Domain position: 71
• Structural Position: 103
• Q(SASA): 0.2344
• 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	rs767070836	-1.446	0.994	N	0.561	0.535	0.479518371956	gnomAD-2.1.1	1.21E-05	None	None	None	None	N	None	0	0	None	0	0	None	9.81E-05	None	0	0	0
E/A	rs767070836	-1.446	0.994	N	0.561	0.535	0.479518371956	gnomAD-4.0.0	1.11453E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.00301E-04	0
E/K	rs1706025148	None	0.989	N	0.462	0.334	0.4018988957	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
E/K	rs1706025148	None	0.989	N	0.462	0.334	0.4018988957	gnomAD-4.0.0	1.5225E-05	None	None	None	None	N	None	6.98983E-05	0	None	0	0	None	0	0	1.32544E-05	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	0.2539	likely_benign	0.232	benign	-1.048	Destabilizing	0.994	D	0.561	neutral	N	0.482777997	None	None	N
E/C	0.853	likely_pathogenic	0.8164	pathogenic	-0.551	Destabilizing	1.0	D	0.749	deleterious	None	None	None	None	N
E/D	0.1556	likely_benign	0.1423	benign	-1.383	Destabilizing	0.217	N	0.197	neutral	N	0.474864731	None	None	N
E/F	0.6961	likely_pathogenic	0.6726	pathogenic	-0.407	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
E/G	0.4051	ambiguous	0.3882	ambiguous	-1.495	Destabilizing	0.989	D	0.635	neutral	N	0.491603088	None	None	N
E/H	0.6029	likely_pathogenic	0.5714	pathogenic	-0.679	Destabilizing	0.999	D	0.637	neutral	None	None	None	None	N
E/I	0.4341	ambiguous	0.4084	ambiguous	0.211	Stabilizing	1.0	D	0.82	deleterious	None	None	None	None	N
E/K	0.439	ambiguous	0.4311	ambiguous	-1.143	Destabilizing	0.989	D	0.462	neutral	N	0.467912518	None	None	N
E/L	0.4467	ambiguous	0.4498	ambiguous	0.211	Stabilizing	0.999	D	0.788	deleterious	None	None	None	None	N
E/M	0.4888	ambiguous	0.4641	ambiguous	0.907	Stabilizing	1.0	D	0.761	deleterious	None	None	None	None	N
E/N	0.3816	ambiguous	0.3254	benign	-1.57	Destabilizing	0.784	D	0.247	neutral	None	None	None	None	N
E/P	0.8712	likely_pathogenic	0.8847	pathogenic	-0.189	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
E/Q	0.2287	likely_benign	0.2102	benign	-1.315	Destabilizing	0.998	D	0.603	neutral	N	0.467938971	None	None	N
E/R	0.5938	likely_pathogenic	0.578	pathogenic	-0.915	Destabilizing	0.999	D	0.625	neutral	None	None	None	None	N
E/S	0.2806	likely_benign	0.2419	benign	-2.118	Highly Destabilizing	0.992	D	0.451	neutral	None	None	None	None	N
E/T	0.3241	likely_benign	0.2924	benign	-1.726	Destabilizing	0.992	D	0.681	prob.neutral	None	None	None	None	N
E/V	0.2977	likely_benign	0.2794	benign	-0.189	Destabilizing	0.999	D	0.777	deleterious	N	0.477866926	None	None	N
E/W	0.9088	likely_pathogenic	0.8971	pathogenic	-0.28	Destabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	N
E/Y	0.6214	likely_pathogenic	0.5756	pathogenic	-0.171	Destabilizing	1.0	D	0.789	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.