TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27744	83455;83456;83457	chr2:178562902;178562901;178562900	chr2:179427629;179427628;179427627
N2AB	26103	78532;78533;78534	chr2:178562902;178562901;178562900	chr2:179427629;179427628;179427627
N2A	25176	75751;75752;75753	chr2:178562902;178562901;178562900	chr2:179427629;179427628;179427627
N2B	18679	56260;56261;56262	chr2:178562902;178562901;178562900	chr2:179427629;179427628;179427627
Novex-1	18804	56635;56636;56637	chr2:178562902;178562901;178562900	chr2:179427629;179427628;179427627
Novex-2	18871	56836;56837;56838	chr2:178562902;178562901;178562900	chr2:179427629;179427628;179427627
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Ig-141
• Domain position: 69
• Structural Position: 154
• Q(SASA): 0.2138
• 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	1.0	D	0.802	0.844	0.75324538058	gnomAD-4.0.0	1.59196E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85878E-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	0.9993	likely_pathogenic	0.9993	pathogenic	-2.551	Highly Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
Y/C	0.9775	likely_pathogenic	0.9777	pathogenic	-1.795	Destabilizing	1.0	D	0.84	deleterious	D	0.652262572	None	None	N
Y/D	0.9991	likely_pathogenic	0.9992	pathogenic	-3.409	Highly Destabilizing	1.0	D	0.875	deleterious	D	0.652262572	None	None	N
Y/E	0.9996	likely_pathogenic	0.9996	pathogenic	-3.163	Highly Destabilizing	1.0	D	0.878	deleterious	None	None	None	None	N
Y/F	0.2637	likely_benign	0.2724	benign	-0.979	Destabilizing	0.999	D	0.723	prob.delet.	D	0.601752478	None	None	N
Y/G	0.9973	likely_pathogenic	0.9974	pathogenic	-3.004	Highly Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	N
Y/H	0.9879	likely_pathogenic	0.9887	pathogenic	-2.338	Highly Destabilizing	1.0	D	0.802	deleterious	D	0.652060768	None	None	N
Y/I	0.9766	likely_pathogenic	0.9776	pathogenic	-1.041	Destabilizing	1.0	D	0.854	deleterious	None	None	None	None	N
Y/K	0.9994	likely_pathogenic	0.9994	pathogenic	-2.261	Highly Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	N
Y/L	0.9514	likely_pathogenic	0.9516	pathogenic	-1.041	Destabilizing	0.999	D	0.779	deleterious	None	None	None	None	N
Y/M	0.9909	likely_pathogenic	0.9913	pathogenic	-1.044	Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
Y/N	0.9945	likely_pathogenic	0.9949	pathogenic	-3.254	Highly Destabilizing	1.0	D	0.859	deleterious	D	0.652262572	None	None	N
Y/P	0.9996	likely_pathogenic	0.9996	pathogenic	-1.562	Destabilizing	1.0	D	0.893	deleterious	None	None	None	None	N
Y/Q	0.9994	likely_pathogenic	0.9995	pathogenic	-2.795	Highly Destabilizing	1.0	D	0.83	deleterious	None	None	None	None	N
Y/R	0.9977	likely_pathogenic	0.9978	pathogenic	-2.485	Highly Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
Y/S	0.9977	likely_pathogenic	0.9978	pathogenic	-3.492	Highly Destabilizing	1.0	D	0.877	deleterious	D	0.652262572	None	None	N
Y/T	0.9991	likely_pathogenic	0.9992	pathogenic	-3.097	Highly Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	N
Y/V	0.9736	likely_pathogenic	0.9753	pathogenic	-1.562	Destabilizing	1.0	D	0.814	deleterious	None	None	None	None	N
Y/W	0.8173	likely_pathogenic	0.8185	pathogenic	-0.385	Destabilizing	1.0	D	0.791	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.