TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17934	54025;54026;54027	chr2:178605495;178605494;178605493	chr2:179470222;179470221;179470220
N2AB	16293	49102;49103;49104	chr2:178605495;178605494;178605493	chr2:179470222;179470221;179470220
N2A	15366	46321;46322;46323	chr2:178605495;178605494;178605493	chr2:179470222;179470221;179470220
N2B	8869	26830;26831;26832	chr2:178605495;178605494;178605493	chr2:179470222;179470221;179470220
Novex-1	8994	27205;27206;27207	chr2:178605495;178605494;178605493	chr2:179470222;179470221;179470220
Novex-2	9061	27406;27407;27408	chr2:178605495;178605494;178605493	chr2:179470222;179470221;179470220
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: Fn3-18
• Domain position: 73
• Structural Position: 105
• Q(SASA): 0.1094
• 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	rs774287393	-2.675	0.999	N	0.59	0.295	0.353548585375	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
E/K	rs774287393	-2.675	0.999	N	0.59	0.295	0.353548585375	gnomAD-4.0.0	1.59461E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43526E-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	0.6448	likely_pathogenic	0.6814	pathogenic	-1.414	Destabilizing	0.999	D	0.732	prob.delet.	N	0.471764086	None	None	N
E/C	0.9697	likely_pathogenic	0.9725	pathogenic	-0.775	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
E/D	0.5482	ambiguous	0.7055	pathogenic	-1.693	Destabilizing	0.999	D	0.591	neutral	D	0.526333068	None	None	N
E/F	0.9766	likely_pathogenic	0.984	pathogenic	-0.988	Destabilizing	1.0	D	0.854	deleterious	None	None	None	None	N
E/G	0.8322	likely_pathogenic	0.856	pathogenic	-1.833	Destabilizing	1.0	D	0.777	deleterious	N	0.486767696	None	None	N
E/H	0.9342	likely_pathogenic	0.9508	pathogenic	-1.059	Destabilizing	1.0	D	0.635	neutral	None	None	None	None	N
E/I	0.8396	likely_pathogenic	0.8703	pathogenic	-0.208	Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
E/K	0.8944	likely_pathogenic	0.9182	pathogenic	-1.638	Destabilizing	0.999	D	0.59	neutral	N	0.497740957	None	None	N
E/L	0.9069	likely_pathogenic	0.9395	pathogenic	-0.208	Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	N
E/M	0.8837	likely_pathogenic	0.9103	pathogenic	0.571	Stabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
E/N	0.8622	likely_pathogenic	0.9113	pathogenic	-1.926	Destabilizing	1.0	D	0.677	prob.neutral	None	None	None	None	N
E/P	0.9972	likely_pathogenic	0.9981	pathogenic	-0.595	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	N
E/Q	0.5176	ambiguous	0.5296	ambiguous	-1.585	Destabilizing	1.0	D	0.684	prob.neutral	N	0.462628306	None	None	N
E/R	0.9007	likely_pathogenic	0.9211	pathogenic	-1.476	Destabilizing	1.0	D	0.676	prob.neutral	None	None	None	None	N
E/S	0.683	likely_pathogenic	0.7282	pathogenic	-2.559	Highly Destabilizing	0.999	D	0.647	neutral	None	None	None	None	N
E/T	0.7513	likely_pathogenic	0.7829	pathogenic	-2.168	Highly Destabilizing	1.0	D	0.759	deleterious	None	None	None	None	N
E/V	0.7004	likely_pathogenic	0.7468	pathogenic	-0.595	Destabilizing	1.0	D	0.781	deleterious	N	0.518385588	None	None	N
E/W	0.9917	likely_pathogenic	0.9953	pathogenic	-1.083	Destabilizing	1.0	D	0.814	deleterious	None	None	None	None	N
E/Y	0.9577	likely_pathogenic	0.9728	pathogenic	-0.84	Destabilizing	1.0	D	0.811	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.