TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26155	78688;78689;78690	chr2:178567669;178567668;178567667	chr2:179432396;179432395;179432394
N2AB	24514	73765;73766;73767	chr2:178567669;178567668;178567667	chr2:179432396;179432395;179432394
N2A	23587	70984;70985;70986	chr2:178567669;178567668;178567667	chr2:179432396;179432395;179432394
N2B	17090	51493;51494;51495	chr2:178567669;178567668;178567667	chr2:179432396;179432395;179432394
Novex-1	17215	51868;51869;51870	chr2:178567669;178567668;178567667	chr2:179432396;179432395;179432394
Novex-2	17282	52069;52070;52071	chr2:178567669;178567668;178567667	chr2:179432396;179432395;179432394
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: Fn3-78
• Domain position: 68
• Structural Position: 99
• Q(SASA): 0.4169
• 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/K	rs778395291	0.129	0.999	N	0.705	0.356	0.436993770938	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.28E-05	None	0	0	0
E/K	rs778395291	0.129	0.999	N	0.705	0.356	0.436993770938	gnomAD-4.0.0	1.59479E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43534E-05	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	0.3154	likely_benign	0.3116	benign	-0.38	Destabilizing	0.999	D	0.68	prob.neutral	N	0.473708961	None	None	N
E/C	0.9757	likely_pathogenic	0.9727	pathogenic	0.048	Stabilizing	1.0	D	0.711	prob.delet.	None	None	None	None	N
E/D	0.6614	likely_pathogenic	0.6293	pathogenic	-0.773	Destabilizing	0.999	D	0.581	neutral	N	0.492893308	None	None	N
E/F	0.9806	likely_pathogenic	0.9774	pathogenic	-0.53	Destabilizing	1.0	D	0.724	prob.delet.	None	None	None	None	N
E/G	0.5027	ambiguous	0.4769	ambiguous	-0.627	Destabilizing	1.0	D	0.673	neutral	N	0.495615559	None	None	N
E/H	0.9357	likely_pathogenic	0.924	pathogenic	-0.769	Destabilizing	1.0	D	0.699	prob.neutral	None	None	None	None	N
E/I	0.7591	likely_pathogenic	0.7519	pathogenic	0.246	Stabilizing	1.0	D	0.713	prob.delet.	None	None	None	None	N
E/K	0.4783	ambiguous	0.4436	ambiguous	-0.047	Destabilizing	0.999	D	0.705	prob.neutral	N	0.485954321	None	None	N
E/L	0.86	likely_pathogenic	0.8478	pathogenic	0.246	Stabilizing	1.0	D	0.703	prob.neutral	None	None	None	None	N
E/M	0.8019	likely_pathogenic	0.7919	pathogenic	0.607	Stabilizing	1.0	D	0.68	prob.neutral	None	None	None	None	N
E/N	0.7971	likely_pathogenic	0.7769	pathogenic	-0.214	Destabilizing	1.0	D	0.728	prob.delet.	None	None	None	None	N
E/P	0.7696	likely_pathogenic	0.7586	pathogenic	0.059	Stabilizing	1.0	D	0.691	prob.neutral	None	None	None	None	N
E/Q	0.3314	likely_benign	0.3199	benign	-0.191	Destabilizing	1.0	D	0.692	prob.neutral	N	0.476991098	None	None	N
E/R	0.6917	likely_pathogenic	0.6586	pathogenic	-0.001	Destabilizing	1.0	D	0.722	prob.delet.	None	None	None	None	N
E/S	0.5675	likely_pathogenic	0.5478	ambiguous	-0.428	Destabilizing	0.999	D	0.719	prob.delet.	None	None	None	None	N
E/T	0.6284	likely_pathogenic	0.6108	pathogenic	-0.242	Destabilizing	1.0	D	0.713	prob.delet.	None	None	None	None	N
E/V	0.5364	ambiguous	0.5298	ambiguous	0.059	Stabilizing	1.0	D	0.684	prob.neutral	N	0.48861412	None	None	N
E/W	0.9956	likely_pathogenic	0.9945	pathogenic	-0.511	Destabilizing	1.0	D	0.712	prob.delet.	None	None	None	None	N
E/Y	0.9733	likely_pathogenic	0.9692	pathogenic	-0.323	Destabilizing	1.0	D	0.697	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.