TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20091	60496;60497;60498	chr2:178591454;178591453;178591452	chr2:179456181;179456180;179456179
N2AB	18450	55573;55574;55575	chr2:178591454;178591453;178591452	chr2:179456181;179456180;179456179
N2A	17523	52792;52793;52794	chr2:178591454;178591453;178591452	chr2:179456181;179456180;179456179
N2B	11026	33301;33302;33303	chr2:178591454;178591453;178591452	chr2:179456181;179456180;179456179
Novex-1	11151	33676;33677;33678	chr2:178591454;178591453;178591452	chr2:179456181;179456180;179456179
Novex-2	11218	33877;33878;33879	chr2:178591454;178591453;178591452	chr2:179456181;179456180;179456179
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Ig-120
• Domain position: 12
• Structural Position: 18
• Q(SASA): 0.9164
• 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/N	rs775961664	0.123	1.0	D	0.722	0.384	0.31077124679	gnomAD-2.1.1	4.29E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.78E-05	None	0	0	0
K/N	rs775961664	0.123	1.0	D	0.722	0.384	0.31077124679	gnomAD-4.0.0	1.38387E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	2.41371E-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
K/A	0.8446	likely_pathogenic	0.8369	pathogenic	-0.007	Destabilizing	0.999	D	0.698	prob.neutral	None	None	None	None	N
K/C	0.9417	likely_pathogenic	0.9302	pathogenic	-0.392	Destabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	N
K/D	0.9518	likely_pathogenic	0.9551	pathogenic	0.006	Stabilizing	1.0	D	0.696	prob.neutral	None	None	None	None	N
K/E	0.6619	likely_pathogenic	0.6754	pathogenic	0.024	Stabilizing	0.999	D	0.725	prob.delet.	D	0.523938629	None	None	N
K/F	0.9716	likely_pathogenic	0.9694	pathogenic	-0.189	Destabilizing	1.0	D	0.703	prob.neutral	None	None	None	None	N
K/G	0.9197	likely_pathogenic	0.9196	pathogenic	-0.206	Destabilizing	1.0	D	0.659	neutral	None	None	None	None	N
K/H	0.5951	likely_pathogenic	0.5876	pathogenic	-0.374	Destabilizing	1.0	D	0.646	neutral	None	None	None	None	N
K/I	0.849	likely_pathogenic	0.8379	pathogenic	0.441	Stabilizing	1.0	D	0.707	prob.neutral	None	None	None	None	N
K/L	0.7568	likely_pathogenic	0.7442	pathogenic	0.441	Stabilizing	1.0	D	0.659	neutral	None	None	None	None	N
K/M	0.6369	likely_pathogenic	0.6387	pathogenic	0.083	Stabilizing	1.0	D	0.643	neutral	D	0.53583049	None	None	N
K/N	0.886	likely_pathogenic	0.8925	pathogenic	0.006	Stabilizing	1.0	D	0.722	prob.delet.	D	0.525805498	None	None	N
K/P	0.8533	likely_pathogenic	0.8457	pathogenic	0.319	Stabilizing	1.0	D	0.661	neutral	None	None	None	None	N
K/Q	0.3508	ambiguous	0.3445	ambiguous	-0.112	Destabilizing	1.0	D	0.714	prob.delet.	D	0.5262855	None	None	N
K/R	0.1004	likely_benign	0.0948	benign	-0.108	Destabilizing	0.999	D	0.656	neutral	N	0.445824562	None	None	N
K/S	0.8978	likely_pathogenic	0.8972	pathogenic	-0.45	Destabilizing	0.999	D	0.716	prob.delet.	None	None	None	None	N
K/T	0.6451	likely_pathogenic	0.6512	pathogenic	-0.282	Destabilizing	1.0	D	0.679	prob.neutral	N	0.511086762	None	None	N
K/V	0.7964	likely_pathogenic	0.7841	pathogenic	0.319	Stabilizing	1.0	D	0.697	prob.neutral	None	None	None	None	N
K/W	0.949	likely_pathogenic	0.9456	pathogenic	-0.234	Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	N
K/Y	0.9146	likely_pathogenic	0.9147	pathogenic	0.119	Stabilizing	1.0	D	0.691	prob.neutral	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.