TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18698	56317;56318;56319	chr2:178599809;178599808;178599807	chr2:179464536;179464535;179464534
N2AB	17057	51394;51395;51396	chr2:178599809;178599808;178599807	chr2:179464536;179464535;179464534
N2A	16130	48613;48614;48615	chr2:178599809;178599808;178599807	chr2:179464536;179464535;179464534
N2B	9633	29122;29123;29124	chr2:178599809;178599808;178599807	chr2:179464536;179464535;179464534
Novex-1	9758	29497;29498;29499	chr2:178599809;178599808;178599807	chr2:179464536;179464535;179464534
Novex-2	9825	29698;29699;29700	chr2:178599809;178599808;178599807	chr2:179464536;179464535;179464534
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: Ig-116
• Domain position: 11
• Structural Position: 23
• Q(SASA): 0.3598
• 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/D	None	None	0.999	N	0.462	0.254	0.316788114976	gnomAD-4.0.0	1.37783E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.80515E-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	0.2522	likely_benign	0.2281	benign	-0.802	Destabilizing	0.999	D	0.627	neutral	N	0.453189598	None	None	N
E/C	0.9483	likely_pathogenic	0.9493	pathogenic	-0.156	Destabilizing	1.0	D	0.749	deleterious	None	None	None	None	N
E/D	0.5117	ambiguous	0.5806	pathogenic	-0.764	Destabilizing	0.999	D	0.462	neutral	N	0.510296462	None	None	N
E/F	0.9549	likely_pathogenic	0.9548	pathogenic	-0.757	Destabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	N
E/G	0.5392	ambiguous	0.564	ambiguous	-1.051	Destabilizing	1.0	D	0.691	prob.neutral	N	0.490475954	None	None	N
E/H	0.8695	likely_pathogenic	0.8808	pathogenic	-0.896	Destabilizing	1.0	D	0.676	prob.neutral	None	None	None	None	N
E/I	0.6351	likely_pathogenic	0.6233	pathogenic	-0.156	Destabilizing	1.0	D	0.763	deleterious	None	None	None	None	N
E/K	0.4763	ambiguous	0.5209	ambiguous	-0.077	Destabilizing	0.999	D	0.609	neutral	N	0.498116598	None	None	N
E/L	0.7529	likely_pathogenic	0.7612	pathogenic	-0.156	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	N
E/M	0.7107	likely_pathogenic	0.6821	pathogenic	0.277	Stabilizing	1.0	D	0.697	prob.neutral	None	None	None	None	N
E/N	0.6776	likely_pathogenic	0.7014	pathogenic	-0.387	Destabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	N
E/P	0.9309	likely_pathogenic	0.9593	pathogenic	-0.352	Destabilizing	1.0	D	0.689	prob.neutral	None	None	None	None	N
E/Q	0.279	likely_benign	0.2716	benign	-0.369	Destabilizing	1.0	D	0.639	neutral	N	0.480320271	None	None	N
E/R	0.6544	likely_pathogenic	0.6904	pathogenic	0.023	Stabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	N
E/S	0.5001	ambiguous	0.4911	ambiguous	-0.609	Destabilizing	0.999	D	0.663	neutral	None	None	None	None	N
E/T	0.551	ambiguous	0.5591	ambiguous	-0.406	Destabilizing	1.0	D	0.723	prob.delet.	None	None	None	None	N
E/V	0.4296	ambiguous	0.4121	ambiguous	-0.352	Destabilizing	1.0	D	0.733	prob.delet.	N	0.475469025	None	None	N
E/W	0.9864	likely_pathogenic	0.9888	pathogenic	-0.585	Destabilizing	1.0	D	0.75	deleterious	None	None	None	None	N
E/Y	0.9118	likely_pathogenic	0.9217	pathogenic	-0.509	Destabilizing	1.0	D	0.722	prob.delet.	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.