TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14036	42331;42332;42333	chr2:178634768;178634767;178634766	chr2:179499495;179499494;179499493
N2AB	12395	37408;37409;37410	chr2:178634768;178634767;178634766	chr2:179499495;179499494;179499493
N2A	11468	34627;34628;34629	chr2:178634768;178634767;178634766	chr2:179499495;179499494;179499493
N2B	4971	15136;15137;15138	chr2:178634768;178634767;178634766	chr2:179499495;179499494;179499493
Novex-1	5096	15511;15512;15513	chr2:178634768;178634767;178634766	chr2:179499495;179499494;179499493
Novex-2	5163	15712;15713;15714	chr2:178634768;178634767;178634766	chr2:179499495;179499494;179499493
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAC
• RefSeq wild type template codon: ATG
• Domain: Ig-90
• Domain position: 72
• Structural Position: 156
• Q(SASA): 0.0981
• 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
Y/H	None	None	0.999	N	0.794	0.471	0.337868961071	gnomAD-4.0.0	3.18513E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.72164E-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
Y/A	0.9977	likely_pathogenic	0.9962	pathogenic	-2.809	Highly Destabilizing	0.999	D	0.732	deleterious	None	None	None	None	N
Y/C	0.9056	likely_pathogenic	0.8414	pathogenic	-1.284	Destabilizing	1.0	D	0.809	deleterious	N	0.395647522	None	None	N
Y/D	0.9987	likely_pathogenic	0.9977	pathogenic	-3.297	Highly Destabilizing	0.999	D	0.881	deleterious	N	0.411137144	None	None	N
Y/E	0.9995	likely_pathogenic	0.999	pathogenic	-3.079	Highly Destabilizing	0.999	D	0.859	deleterious	None	None	None	None	N
Y/F	0.2018	likely_benign	0.1213	benign	-0.96	Destabilizing	0.997	D	0.505	neutral	N	0.418921636	None	None	N
Y/G	0.9929	likely_pathogenic	0.99	pathogenic	-3.221	Highly Destabilizing	0.999	D	0.875	deleterious	None	None	None	None	N
Y/H	0.9892	likely_pathogenic	0.9747	pathogenic	-1.98	Destabilizing	0.999	D	0.794	deleterious	N	0.411137144	None	None	N
Y/I	0.9792	likely_pathogenic	0.9597	pathogenic	-1.436	Destabilizing	0.999	D	0.82	deleterious	None	None	None	None	N
Y/K	0.9995	likely_pathogenic	0.9989	pathogenic	-1.98	Destabilizing	0.999	D	0.86	deleterious	None	None	None	None	N
Y/L	0.8807	likely_pathogenic	0.8676	pathogenic	-1.436	Destabilizing	0.998	D	0.634	neutral	None	None	None	None	N
Y/M	0.9851	likely_pathogenic	0.9751	pathogenic	-1.086	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	N
Y/N	0.9945	likely_pathogenic	0.9899	pathogenic	-2.82	Highly Destabilizing	0.999	D	0.862	deleterious	N	0.411137144	None	None	N
Y/P	0.9993	likely_pathogenic	0.9988	pathogenic	-1.909	Destabilizing	0.999	D	0.899	deleterious	None	None	None	None	N
Y/Q	0.9992	likely_pathogenic	0.9982	pathogenic	-2.533	Highly Destabilizing	0.999	D	0.829	deleterious	None	None	None	None	N
Y/R	0.9982	likely_pathogenic	0.9961	pathogenic	-1.883	Destabilizing	0.999	D	0.857	deleterious	None	None	None	None	N
Y/S	0.9951	likely_pathogenic	0.9914	pathogenic	-3.1	Highly Destabilizing	0.999	D	0.863	deleterious	N	0.410661638	None	None	N
Y/T	0.9986	likely_pathogenic	0.9973	pathogenic	-2.762	Highly Destabilizing	0.999	D	0.86	deleterious	None	None	None	None	N
Y/V	0.9689	likely_pathogenic	0.9486	pathogenic	-1.909	Destabilizing	0.999	D	0.688	prob.delet.	None	None	None	None	N
Y/W	0.8901	likely_pathogenic	0.83	pathogenic	-0.279	Destabilizing	1.0	D	0.704	prob.delet.	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.