TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31332	94219;94220;94221	chr2:178547632;178547631;178547630	chr2:179412359;179412358;179412357
N2AB	29691	89296;89297;89298	chr2:178547632;178547631;178547630	chr2:179412359;179412358;179412357
N2A	28764	86515;86516;86517	chr2:178547632;178547631;178547630	chr2:179412359;179412358;179412357
N2B	22267	67024;67025;67026	chr2:178547632;178547631;178547630	chr2:179412359;179412358;179412357
Novex-1	22392	67399;67400;67401	chr2:178547632;178547631;178547630	chr2:179412359;179412358;179412357
Novex-2	22459	67600;67601;67602	chr2:178547632;178547631;178547630	chr2:179412359;179412358;179412357
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: Fn3-116
• Domain position: 25
• Structural Position: 26
• Q(SASA): 0.7561
• 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/V	rs766706869	0.211	0.999	N	0.69	0.358	0.424549175451	gnomAD-2.1.1	1.21E-05	None	None	None	None	N	None	0	0	None	0	0	None	9.8E-05	None	0	0	0
E/V	rs766706869	0.211	0.999	N	0.69	0.358	0.424549175451	gnomAD-4.0.0	9.54675E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.57437E-06	4.29812E-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
E/A	0.1275	likely_benign	0.1232	benign	-0.379	Destabilizing	0.996	D	0.607	neutral	N	0.40744424	None	None	N
E/C	0.7566	likely_pathogenic	0.7481	pathogenic	-0.267	Destabilizing	1.0	D	0.756	deleterious	None	None	None	None	N
E/D	0.1582	likely_benign	0.1588	benign	-0.872	Destabilizing	0.998	D	0.555	neutral	N	0.517500154	None	None	N
E/F	0.6698	likely_pathogenic	0.6712	pathogenic	0.324	Stabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	N
E/G	0.2377	likely_benign	0.2441	benign	-0.725	Destabilizing	0.999	D	0.643	neutral	N	0.455027543	None	None	N
E/H	0.4916	ambiguous	0.4751	ambiguous	0.414	Stabilizing	1.0	D	0.705	prob.neutral	None	None	None	None	N
E/I	0.222	likely_benign	0.2089	benign	0.548	Stabilizing	1.0	D	0.747	deleterious	None	None	None	None	N
E/K	0.1357	likely_benign	0.1312	benign	0.07	Stabilizing	0.998	D	0.587	neutral	N	0.439788732	None	None	N
E/L	0.277	likely_benign	0.2629	benign	0.548	Stabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	N
E/M	0.3405	ambiguous	0.3278	benign	0.654	Stabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	N
E/N	0.299	likely_benign	0.3016	benign	-0.671	Destabilizing	1.0	D	0.714	prob.delet.	None	None	None	None	N
E/P	0.2374	likely_benign	0.2106	benign	0.262	Stabilizing	0.504	D	0.392	neutral	None	None	None	None	N
E/Q	0.1362	likely_benign	0.129	benign	-0.498	Destabilizing	1.0	D	0.683	prob.neutral	N	0.466609974	None	None	N
E/R	0.2566	likely_benign	0.2362	benign	0.436	Stabilizing	1.0	D	0.712	prob.delet.	None	None	None	None	N
E/S	0.2078	likely_benign	0.2086	benign	-0.861	Destabilizing	0.998	D	0.642	neutral	None	None	None	None	N
E/T	0.2249	likely_benign	0.2185	benign	-0.551	Destabilizing	1.0	D	0.705	prob.neutral	None	None	None	None	N
E/V	0.1476	likely_benign	0.1369	benign	0.262	Stabilizing	0.999	D	0.69	prob.neutral	N	0.452160596	None	None	N
E/W	0.9157	likely_pathogenic	0.9166	pathogenic	0.608	Stabilizing	1.0	D	0.75	deleterious	None	None	None	None	N
E/Y	0.5749	likely_pathogenic	0.5914	pathogenic	0.619	Stabilizing	1.0	D	0.749	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.