TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20941	63046;63047;63048	chr2:178588904;178588903;178588902	chr2:179453631;179453630;179453629
N2AB	19300	58123;58124;58125	chr2:178588904;178588903;178588902	chr2:179453631;179453630;179453629
N2A	18373	55342;55343;55344	chr2:178588904;178588903;178588902	chr2:179453631;179453630;179453629
N2B	11876	35851;35852;35853	chr2:178588904;178588903;178588902	chr2:179453631;179453630;179453629
Novex-1	12001	36226;36227;36228	chr2:178588904;178588903;178588902	chr2:179453631;179453630;179453629
Novex-2	12068	36427;36428;36429	chr2:178588904;178588903;178588902	chr2:179453631;179453630;179453629
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: Fn3-39
• Domain position: 78
• Structural Position: 111
• Q(SASA): 0.2586
• 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	rs1480131306	-1.049	0.999	N	0.537	0.399	0.37097340754	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	rs1480131306	-1.049	0.999	N	0.537	0.399	0.37097340754	gnomAD-4.0.0	1.59284E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43312E-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	0.6177	likely_pathogenic	0.5682	pathogenic	-0.548	Destabilizing	0.999	D	0.672	neutral	N	0.468024195	None	None	N
E/C	0.966	likely_pathogenic	0.9598	pathogenic	-0.471	Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
E/D	0.8689	likely_pathogenic	0.8525	pathogenic	-1.312	Destabilizing	0.999	D	0.461	neutral	N	0.513502323	None	None	N
E/F	0.9854	likely_pathogenic	0.9835	pathogenic	-1.023	Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	N
E/G	0.8046	likely_pathogenic	0.7756	pathogenic	-0.84	Destabilizing	1.0	D	0.762	deleterious	N	0.495398068	None	None	N
E/H	0.9561	likely_pathogenic	0.943	pathogenic	-1.202	Destabilizing	1.0	D	0.681	prob.neutral	None	None	None	None	N
E/I	0.772	likely_pathogenic	0.7669	pathogenic	0.223	Stabilizing	1.0	D	0.882	deleterious	None	None	None	None	N
E/K	0.6726	likely_pathogenic	0.5979	pathogenic	-0.523	Destabilizing	0.999	D	0.537	neutral	N	0.466733976	None	None	N
E/L	0.9333	likely_pathogenic	0.9275	pathogenic	0.223	Stabilizing	1.0	D	0.856	deleterious	None	None	None	None	N
E/M	0.8482	likely_pathogenic	0.8271	pathogenic	0.632	Stabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
E/N	0.9154	likely_pathogenic	0.8996	pathogenic	-0.739	Destabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	N
E/P	0.9988	likely_pathogenic	0.9984	pathogenic	-0.013	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
E/Q	0.2896	likely_benign	0.259	benign	-0.638	Destabilizing	1.0	D	0.614	neutral	N	0.512091547	None	None	N
E/R	0.7818	likely_pathogenic	0.7324	pathogenic	-0.607	Destabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	N
E/S	0.7528	likely_pathogenic	0.7174	pathogenic	-1.146	Destabilizing	0.999	D	0.592	neutral	None	None	None	None	N
E/T	0.7516	likely_pathogenic	0.7301	pathogenic	-0.878	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
E/V	0.5177	ambiguous	0.51	ambiguous	-0.013	Destabilizing	1.0	D	0.825	deleterious	N	0.441300523	None	None	N
E/W	0.9964	likely_pathogenic	0.9957	pathogenic	-1.233	Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
E/Y	0.9823	likely_pathogenic	0.977	pathogenic	-0.837	Destabilizing	1.0	D	0.845	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.