TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17185	51778;51779;51780	chr2:178609870;178609869;178609868	chr2:179474597;179474596;179474595
N2AB	15544	46855;46856;46857	chr2:178609870;178609869;178609868	chr2:179474597;179474596;179474595
N2A	14617	44074;44075;44076	chr2:178609870;178609869;178609868	chr2:179474597;179474596;179474595
N2B	8120	24583;24584;24585	chr2:178609870;178609869;178609868	chr2:179474597;179474596;179474595
Novex-1	8245	24958;24959;24960	chr2:178609870;178609869;178609868	chr2:179474597;179474596;179474595
Novex-2	8312	25159;25160;25161	chr2:178609870;178609869;178609868	chr2:179474597;179474596;179474595
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: Fn3-13
• Domain position: 39
• Structural Position: 41
• Q(SASA): 0.0894
• 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/Q	None	None	1.0	N	0.759	0.348	0.359963025489	gnomAD-4.0.0	1.59266E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43332E-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	0.9918	likely_pathogenic	0.9893	pathogenic	-2.189	Highly Destabilizing	0.999	D	0.74	deleterious	D	0.534862262	None	None	N
E/C	0.9978	likely_pathogenic	0.9973	pathogenic	-1.238	Destabilizing	1.0	D	0.82	deleterious	None	None	None	None	N
E/D	0.8846	likely_pathogenic	0.8766	pathogenic	-2.082	Highly Destabilizing	0.999	D	0.679	prob.neutral	N	0.488538441	None	None	N
E/F	0.9994	likely_pathogenic	0.9992	pathogenic	-1.896	Destabilizing	1.0	D	0.858	deleterious	None	None	None	None	N
E/G	0.9885	likely_pathogenic	0.9843	pathogenic	-2.525	Highly Destabilizing	1.0	D	0.803	deleterious	D	0.529888739	None	None	N
E/H	0.9964	likely_pathogenic	0.9954	pathogenic	-1.656	Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	N
E/I	0.9988	likely_pathogenic	0.9987	pathogenic	-1.199	Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
E/K	0.9903	likely_pathogenic	0.9868	pathogenic	-2.145	Highly Destabilizing	0.999	D	0.675	neutral	N	0.507096769	None	None	N
E/L	0.9975	likely_pathogenic	0.997	pathogenic	-1.199	Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
E/M	0.9978	likely_pathogenic	0.9975	pathogenic	-0.426	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
E/N	0.9958	likely_pathogenic	0.9951	pathogenic	-2.266	Highly Destabilizing	1.0	D	0.788	deleterious	None	None	None	None	N
E/P	0.9999	likely_pathogenic	0.9999	pathogenic	-1.52	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
E/Q	0.9305	likely_pathogenic	0.9118	pathogenic	-1.988	Destabilizing	1.0	D	0.759	deleterious	N	0.4712042	None	None	N
E/R	0.9908	likely_pathogenic	0.9886	pathogenic	-1.882	Destabilizing	1.0	D	0.786	deleterious	None	None	None	None	N
E/S	0.9854	likely_pathogenic	0.9812	pathogenic	-2.886	Highly Destabilizing	0.999	D	0.722	prob.delet.	None	None	None	None	N
E/T	0.9957	likely_pathogenic	0.9946	pathogenic	-2.557	Highly Destabilizing	1.0	D	0.798	deleterious	None	None	None	None	N
E/V	0.9959	likely_pathogenic	0.9952	pathogenic	-1.52	Destabilizing	1.0	D	0.809	deleterious	N	0.52048099	None	None	N
E/W	0.9991	likely_pathogenic	0.999	pathogenic	-1.978	Destabilizing	1.0	D	0.82	deleterious	None	None	None	None	N
E/Y	0.9983	likely_pathogenic	0.9979	pathogenic	-1.771	Destabilizing	1.0	D	0.833	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.