TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25342	76249;76250;76251	chr2:178570108;178570107;178570106	chr2:179434835;179434834;179434833
N2AB	23701	71326;71327;71328	chr2:178570108;178570107;178570106	chr2:179434835;179434834;179434833
N2A	22774	68545;68546;68547	chr2:178570108;178570107;178570106	chr2:179434835;179434834;179434833
N2B	16277	49054;49055;49056	chr2:178570108;178570107;178570106	chr2:179434835;179434834;179434833
Novex-1	16402	49429;49430;49431	chr2:178570108;178570107;178570106	chr2:179434835;179434834;179434833
Novex-2	16469	49630;49631;49632	chr2:178570108;178570107;178570106	chr2:179434835;179434834;179434833
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: Fn3-72
• Domain position: 39
• Structural Position: 41
• Q(SASA): 0.145
• 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	rs762672000	-1.796	1.0	N	0.739	0.346	0.363158594168	gnomAD-2.1.1	1.21E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	2.67E-05	0
E/Q	rs762672000	-1.796	1.0	N	0.739	0.346	0.363158594168	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
E/Q	rs762672000	-1.796	1.0	N	0.739	0.346	0.363158594168	gnomAD-4.0.0	3.84524E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	7.18236E-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	0.9289	likely_pathogenic	0.8913	pathogenic	-1.962	Destabilizing	0.999	D	0.688	prob.neutral	D	0.535026846	None	None	N
E/C	0.9877	likely_pathogenic	0.9838	pathogenic	-1.098	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
E/D	0.7655	likely_pathogenic	0.7141	pathogenic	-1.659	Destabilizing	0.999	D	0.632	neutral	N	0.493969718	None	None	N
E/F	0.9921	likely_pathogenic	0.987	pathogenic	-1.608	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
E/G	0.9338	likely_pathogenic	0.892	pathogenic	-2.348	Highly Destabilizing	1.0	D	0.778	deleterious	D	0.525444968	None	None	N
E/H	0.9674	likely_pathogenic	0.9592	pathogenic	-1.516	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
E/I	0.9845	likely_pathogenic	0.9767	pathogenic	-0.846	Destabilizing	1.0	D	0.824	deleterious	None	None	None	None	N
E/K	0.9594	likely_pathogenic	0.939	pathogenic	-1.918	Destabilizing	0.999	D	0.671	neutral	N	0.515819728	None	None	N
E/L	0.971	likely_pathogenic	0.9537	pathogenic	-0.846	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
E/M	0.9738	likely_pathogenic	0.9587	pathogenic	-0.043	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
E/N	0.9743	likely_pathogenic	0.9615	pathogenic	-2.038	Highly Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
E/P	0.9997	likely_pathogenic	0.9996	pathogenic	-1.206	Destabilizing	1.0	D	0.788	deleterious	None	None	None	None	N
E/Q	0.6209	likely_pathogenic	0.5469	ambiguous	-1.762	Destabilizing	1.0	D	0.739	prob.delet.	N	0.480585496	None	None	N
E/R	0.9599	likely_pathogenic	0.9459	pathogenic	-1.667	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
E/S	0.9285	likely_pathogenic	0.8971	pathogenic	-2.759	Highly Destabilizing	0.999	D	0.727	prob.delet.	None	None	None	None	N
E/T	0.9701	likely_pathogenic	0.9559	pathogenic	-2.396	Highly Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	N
E/V	0.9552	likely_pathogenic	0.9341	pathogenic	-1.206	Destabilizing	1.0	D	0.779	deleterious	D	0.535787315	None	None	N
E/W	0.9931	likely_pathogenic	0.9905	pathogenic	-1.626	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
E/Y	0.9849	likely_pathogenic	0.9793	pathogenic	-1.436	Destabilizing	1.0	D	0.803	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.