TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14012	42259;42260;42261	chr2:178634840;178634839;178634838	chr2:179499567;179499566;179499565
N2AB	12371	37336;37337;37338	chr2:178634840;178634839;178634838	chr2:179499567;179499566;179499565
N2A	11444	34555;34556;34557	chr2:178634840;178634839;178634838	chr2:179499567;179499566;179499565
N2B	4947	15064;15065;15066	chr2:178634840;178634839;178634838	chr2:179499567;179499566;179499565
Novex-1	5072	15439;15440;15441	chr2:178634840;178634839;178634838	chr2:179499567;179499566;179499565
Novex-2	5139	15640;15641;15642	chr2:178634840;178634839;178634838	chr2:179499567;179499566;179499565
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Ig-90
• Domain position: 48
• Structural Position: 123
• Q(SASA): 0.333
• 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
I/V	rs1425644741	None	0.985	N	0.321	0.188	0.394837016283	gnomAD-4.0.0	6.42164E-06	None	None	None	None	N	None	0	2.36507E-05	None	0	0	None	0	0	5.74142E-06	0	3.04414E-05

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
I/A	0.9805	likely_pathogenic	0.9448	pathogenic	-2.056	Highly Destabilizing	0.998	D	0.571	neutral	None	None	None	None	N
I/C	0.9929	likely_pathogenic	0.9784	pathogenic	-1.133	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	N
I/D	0.9977	likely_pathogenic	0.9915	pathogenic	-1.736	Destabilizing	0.999	D	0.791	deleterious	None	None	None	None	N
I/E	0.9791	likely_pathogenic	0.9545	pathogenic	-1.666	Destabilizing	0.999	D	0.785	deleterious	None	None	None	None	N
I/F	0.7556	likely_pathogenic	0.5462	ambiguous	-1.378	Destabilizing	0.999	D	0.725	deleterious	N	0.429693322	None	None	N
I/G	0.9961	likely_pathogenic	0.9863	pathogenic	-2.46	Highly Destabilizing	0.999	D	0.79	deleterious	None	None	None	None	N
I/H	0.9951	likely_pathogenic	0.9816	pathogenic	-1.776	Destabilizing	1.0	D	0.782	deleterious	None	None	None	None	N
I/K	0.9878	likely_pathogenic	0.962	pathogenic	-1.467	Destabilizing	0.999	D	0.789	deleterious	None	None	None	None	N
I/L	0.6003	likely_pathogenic	0.3871	ambiguous	-0.97	Destabilizing	0.985	D	0.329	neutral	N	0.431775142	None	None	N
I/M	0.2964	likely_benign	0.1736	benign	-0.696	Destabilizing	0.999	D	0.703	prob.delet.	N	0.436321918	None	None	N
I/N	0.9672	likely_pathogenic	0.9039	pathogenic	-1.336	Destabilizing	0.999	D	0.796	deleterious	D	0.528461033	None	None	N
I/P	0.9982	likely_pathogenic	0.993	pathogenic	-1.305	Destabilizing	0.999	D	0.8	deleterious	None	None	None	None	N
I/Q	0.9776	likely_pathogenic	0.9362	pathogenic	-1.435	Destabilizing	1.0	D	0.776	deleterious	None	None	None	None	N
I/R	0.9854	likely_pathogenic	0.9533	pathogenic	-0.945	Destabilizing	0.999	D	0.798	deleterious	None	None	None	None	N
I/S	0.9809	likely_pathogenic	0.9371	pathogenic	-1.967	Destabilizing	0.999	D	0.752	deleterious	D	0.526413773	None	None	N
I/T	0.9534	likely_pathogenic	0.9117	pathogenic	-1.774	Destabilizing	0.999	D	0.735	deleterious	N	0.48393189	None	None	N
I/V	0.4383	ambiguous	0.3115	benign	-1.305	Destabilizing	0.985	D	0.321	neutral	N	0.423337162	None	None	N
I/W	0.9872	likely_pathogenic	0.9639	pathogenic	-1.565	Destabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	N
I/Y	0.9616	likely_pathogenic	0.8952	pathogenic	-1.329	Destabilizing	0.999	D	0.787	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.