TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3003	9232;9233;9234	chr2:178768829;178768828;178768827	chr2:179633556;179633555;179633554
N2AB	3003	9232;9233;9234	chr2:178768829;178768828;178768827	chr2:179633556;179633555;179633554
N2A	3003	9232;9233;9234	chr2:178768829;178768828;178768827	chr2:179633556;179633555;179633554
N2B	2957	9094;9095;9096	chr2:178768829;178768828;178768827	chr2:179633556;179633555;179633554
Novex-1	2957	9094;9095;9096	chr2:178768829;178768828;178768827	chr2:179633556;179633555;179633554
Novex-2	2957	9094;9095;9096	chr2:178768829;178768828;178768827	chr2:179633556;179633555;179633554
Novex-3	3003	9232;9233;9234	chr2:178768829;178768828;178768827	chr2:179633556;179633555;179633554

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Ig-20
• Domain position: 35
• Structural Position: 50
• Q(SASA): 0.1046
• 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
K/Q	None	None	1.0	D	0.659	0.573	0.286848849266	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
K/A	0.9923	likely_pathogenic	0.992	pathogenic	-0.913	Destabilizing	0.999	D	0.696	prob.neutral	None	None	None	None	N
K/C	0.9715	likely_pathogenic	0.9806	pathogenic	-0.893	Destabilizing	1.0	D	0.814	deleterious	None	None	None	None	N
K/D	0.9992	likely_pathogenic	0.9991	pathogenic	-0.331	Destabilizing	1.0	D	0.759	deleterious	None	None	None	None	N
K/E	0.9859	likely_pathogenic	0.9814	pathogenic	-0.17	Destabilizing	0.999	D	0.609	neutral	D	0.655340675	None	None	N
K/F	0.9954	likely_pathogenic	0.9959	pathogenic	-0.556	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
K/G	0.9964	likely_pathogenic	0.9957	pathogenic	-1.319	Destabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	N
K/H	0.8516	likely_pathogenic	0.8871	pathogenic	-1.649	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	N
K/I	0.9803	likely_pathogenic	0.9779	pathogenic	0.167	Stabilizing	1.0	D	0.816	deleterious	None	None	None	None	N
K/L	0.9596	likely_pathogenic	0.9575	pathogenic	0.167	Stabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	N
K/M	0.9463	likely_pathogenic	0.941	pathogenic	0.043	Stabilizing	1.0	D	0.743	deleterious	D	0.654636067	None	None	N
K/N	0.9951	likely_pathogenic	0.9944	pathogenic	-0.762	Destabilizing	1.0	D	0.683	prob.neutral	D	0.654636067	None	None	N
K/P	0.9995	likely_pathogenic	0.9993	pathogenic	-0.164	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	N
K/Q	0.831	likely_pathogenic	0.8164	pathogenic	-0.747	Destabilizing	1.0	D	0.659	neutral	D	0.653806629	None	None	N
K/R	0.1868	likely_benign	0.1956	benign	-0.7	Destabilizing	0.999	D	0.599	neutral	N	0.493569035	None	None	N
K/S	0.996	likely_pathogenic	0.9953	pathogenic	-1.48	Destabilizing	0.999	D	0.633	neutral	None	None	None	None	N
K/T	0.992	likely_pathogenic	0.9905	pathogenic	-1.086	Destabilizing	1.0	D	0.732	prob.delet.	D	0.653932764	None	None	N
K/V	0.9712	likely_pathogenic	0.9716	pathogenic	-0.164	Destabilizing	1.0	D	0.758	deleterious	None	None	None	None	N
K/W	0.9888	likely_pathogenic	0.9904	pathogenic	-0.422	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
K/Y	0.9739	likely_pathogenic	0.978	pathogenic	-0.109	Destabilizing	1.0	D	0.781	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.