TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27706	83341;83342;83343	chr2:178563016;178563015;178563014	chr2:179427743;179427742;179427741
N2AB	26065	78418;78419;78420	chr2:178563016;178563015;178563014	chr2:179427743;179427742;179427741
N2A	25138	75637;75638;75639	chr2:178563016;178563015;178563014	chr2:179427743;179427742;179427741
N2B	18641	56146;56147;56148	chr2:178563016;178563015;178563014	chr2:179427743;179427742;179427741
Novex-1	18766	56521;56522;56523	chr2:178563016;178563015;178563014	chr2:179427743;179427742;179427741
Novex-2	18833	56722;56723;56724	chr2:178563016;178563015;178563014	chr2:179427743;179427742;179427741
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-141
• Domain position: 31
• Structural Position: 45
• Q(SASA): 0.4202
• 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	rs72648217	0.196	0.287	N	0.329	0.288	0.296679040009	gnomAD-2.1.1	2.01E-05	None	None	None	None	N	None	0	0	None	0	0	None	9.81E-05	None	0	1.78E-05	0
E/K	rs72648217	0.196	0.287	N	0.329	0.288	0.296679040009	gnomAD-3.1.2	2.63E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	2.94E-05	4.1425E-04	0
E/K	rs72648217	0.196	0.287	N	0.329	0.288	0.296679040009	1000 genomes	1.99681E-04	None	None	None	None	N	None	0	0	None	None	0	0	None	None	None	1E-03	None
E/K	rs72648217	0.196	0.287	N	0.329	0.288	0.296679040009	gnomAD-4.0.0	2.29294E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.11921E-05	1.31755E-04	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	0.1268	likely_benign	0.126	benign	-0.369	Destabilizing	0.919	D	0.551	neutral	D	0.529904596	None	None	N
E/C	0.792	likely_pathogenic	0.7988	pathogenic	-0.15	Destabilizing	1.0	D	0.771	deleterious	None	None	None	None	N
E/D	0.1598	likely_benign	0.1515	benign	-0.452	Destabilizing	0.958	D	0.402	neutral	N	0.493974897	None	None	N
E/F	0.7281	likely_pathogenic	0.7303	pathogenic	-0.222	Destabilizing	1.0	D	0.768	deleterious	None	None	None	None	N
E/G	0.2333	likely_benign	0.2403	benign	-0.587	Destabilizing	0.988	D	0.665	neutral	D	0.536819678	None	None	N
E/H	0.3941	ambiguous	0.3981	ambiguous	-0.044	Destabilizing	0.999	D	0.633	neutral	None	None	None	None	N
E/I	0.2325	likely_benign	0.2262	benign	0.178	Stabilizing	0.995	D	0.789	deleterious	None	None	None	None	N
E/K	0.1296	likely_benign	0.1282	benign	0.087	Stabilizing	0.287	N	0.329	neutral	N	0.490884848	None	None	N
E/L	0.3049	likely_benign	0.3086	benign	0.178	Stabilizing	0.991	D	0.744	deleterious	None	None	None	None	N
E/M	0.3508	ambiguous	0.3522	ambiguous	0.217	Stabilizing	1.0	D	0.754	deleterious	None	None	None	None	N
E/N	0.2158	likely_benign	0.2041	benign	-0.167	Destabilizing	0.991	D	0.616	neutral	None	None	None	None	N
E/P	0.9096	likely_pathogenic	0.9064	pathogenic	0.017	Stabilizing	0.995	D	0.737	prob.delet.	None	None	None	None	N
E/Q	0.1218	likely_benign	0.1265	benign	-0.122	Destabilizing	0.983	D	0.531	neutral	N	0.486719968	None	None	N
E/R	0.2332	likely_benign	0.2308	benign	0.345	Stabilizing	0.982	D	0.619	neutral	None	None	None	None	N
E/S	0.1733	likely_benign	0.1698	benign	-0.352	Destabilizing	0.968	D	0.523	neutral	None	None	None	None	N
E/T	0.1466	likely_benign	0.1443	benign	-0.182	Destabilizing	0.991	D	0.683	prob.neutral	None	None	None	None	N
E/V	0.1368	likely_benign	0.1357	benign	0.017	Stabilizing	0.988	D	0.739	prob.delet.	D	0.525133494	None	None	N
E/W	0.9103	likely_pathogenic	0.9132	pathogenic	-0.088	Destabilizing	1.0	D	0.776	deleterious	None	None	None	None	N
E/Y	0.6315	likely_pathogenic	0.6296	pathogenic	0.007	Stabilizing	0.998	D	0.773	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.