TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6192	18799;18800;18801	chr2:178729679;178729678;178729677	chr2:179594406;179594405;179594404
N2AB	5875	17848;17849;17850	chr2:178729679;178729678;178729677	chr2:179594406;179594405;179594404
N2A	4948	15067;15068;15069	chr2:178729679;178729678;178729677	chr2:179594406;179594405;179594404
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-45
• Domain position: 88
• Structural Position: 173
• Q(SASA): 0.5622
• 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
E/K	rs1457411847	-0.082	0.939	N	0.569	0.297	0.342168650903	gnomAD-2.1.1	3.18E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	6.48E-05	0
E/K	rs1457411847	-0.082	0.939	N	0.569	0.297	0.342168650903	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	2.94E-05	0	0
E/K	rs1457411847	-0.082	0.939	N	0.569	0.297	0.342168650903	gnomAD-4.0.0	1.31441E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.94048E-05	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
E/A	0.1373	likely_benign	0.1377	benign	-0.607	Destabilizing	0.939	D	0.671	neutral	N	0.465778546	None	None	N
E/C	0.8163	likely_pathogenic	0.8138	pathogenic	-0.154	Destabilizing	0.999	D	0.722	prob.delet.	None	None	None	None	N
E/D	0.1222	likely_benign	0.1188	benign	-0.526	Destabilizing	0.02	N	0.179	neutral	N	0.457948497	None	None	N
E/F	0.6007	likely_pathogenic	0.6012	pathogenic	-0.308	Destabilizing	0.999	D	0.762	deleterious	None	None	None	None	N
E/G	0.1957	likely_benign	0.1842	benign	-0.852	Destabilizing	0.939	D	0.691	prob.neutral	N	0.486470159	None	None	N
E/H	0.3451	ambiguous	0.3446	ambiguous	-0.211	Destabilizing	0.999	D	0.654	neutral	None	None	None	None	N
E/I	0.2453	likely_benign	0.2547	benign	0.024	Stabilizing	0.993	D	0.788	deleterious	None	None	None	None	N
E/K	0.141	likely_benign	0.1312	benign	0.156	Stabilizing	0.939	D	0.569	neutral	N	0.449384942	None	None	N
E/L	0.2791	likely_benign	0.2838	benign	0.024	Stabilizing	0.993	D	0.771	deleterious	None	None	None	None	N
E/M	0.3374	likely_benign	0.3396	benign	0.235	Stabilizing	0.999	D	0.764	deleterious	None	None	None	None	N
E/N	0.2152	likely_benign	0.2132	benign	-0.297	Destabilizing	0.973	D	0.661	neutral	None	None	None	None	N
E/P	0.6517	likely_pathogenic	0.5692	pathogenic	-0.166	Destabilizing	0.993	D	0.78	deleterious	None	None	None	None	N
E/Q	0.1109	likely_benign	0.1101	benign	-0.237	Destabilizing	0.991	D	0.634	neutral	N	0.476744901	None	None	N
E/R	0.2188	likely_benign	0.2096	benign	0.387	Stabilizing	0.993	D	0.69	prob.neutral	None	None	None	None	N
E/S	0.1804	likely_benign	0.1777	benign	-0.468	Destabilizing	0.953	D	0.578	neutral	None	None	None	None	N
E/T	0.166	likely_benign	0.1637	benign	-0.261	Destabilizing	0.993	D	0.732	prob.delet.	None	None	None	None	N
E/V	0.1597	likely_benign	0.1618	benign	-0.166	Destabilizing	0.991	D	0.77	deleterious	N	0.463778391	None	None	N
E/W	0.8221	likely_pathogenic	0.8206	pathogenic	-0.073	Destabilizing	0.999	D	0.708	prob.delet.	None	None	None	None	N
E/Y	0.4858	ambiguous	0.4868	ambiguous	-0.045	Destabilizing	0.999	D	0.775	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.