TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35360	106303;106304;106305	chr2:178530537;178530536;178530535	chr2:179395264;179395263;179395262
N2AB	33719	101380;101381;101382	chr2:178530537;178530536;178530535	chr2:179395264;179395263;179395262
N2A	32792	98599;98600;98601	chr2:178530537;178530536;178530535	chr2:179395264;179395263;179395262
N2B	26295	79108;79109;79110	chr2:178530537;178530536;178530535	chr2:179395264;179395263;179395262
Novex-1	26420	79483;79484;79485	chr2:178530537;178530536;178530535	chr2:179395264;179395263;179395262
Novex-2	26487	79684;79685;79686	chr2:178530537;178530536;178530535	chr2:179395264;179395263;179395262
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Ig-165
• Domain position: 75
• Structural Position: 157
• Q(SASA): 0.2642
• 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/D	None	None	0.999	N	0.648	0.194	0.299770980665	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
E/Q	None	None	1.0	N	0.753	0.17	0.293502639404	gnomAD-4.0.0	2.05243E-06	None	None	None	None	N	None	0	0	None	0	7.55706E-05	None	0	0	0	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	0.3512	ambiguous	0.3179	benign	-1.155	Destabilizing	0.999	D	0.747	deleterious	N	0.484313658	None	None	N
E/C	0.951	likely_pathogenic	0.9435	pathogenic	-0.746	Destabilizing	1.0	D	0.85	deleterious	None	None	None	None	N
E/D	0.5386	ambiguous	0.5143	ambiguous	-1.44	Destabilizing	0.999	D	0.648	neutral	N	0.486719968	None	None	N
E/F	0.9232	likely_pathogenic	0.9091	pathogenic	-1.074	Destabilizing	1.0	D	0.903	deleterious	None	None	None	None	N
E/G	0.528	ambiguous	0.4893	ambiguous	-1.511	Destabilizing	1.0	D	0.829	deleterious	N	0.500558262	None	None	N
E/H	0.7783	likely_pathogenic	0.75	pathogenic	-1.324	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
E/I	0.5773	likely_pathogenic	0.5262	ambiguous	-0.174	Destabilizing	1.0	D	0.901	deleterious	None	None	None	None	N
E/K	0.3477	ambiguous	0.32	benign	-0.977	Destabilizing	0.999	D	0.707	prob.neutral	N	0.497520031	None	None	N
E/L	0.72	likely_pathogenic	0.6862	pathogenic	-0.174	Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	N
E/M	0.6712	likely_pathogenic	0.6373	pathogenic	0.403	Stabilizing	1.0	D	0.873	deleterious	None	None	None	None	N
E/N	0.6835	likely_pathogenic	0.6495	pathogenic	-1.261	Destabilizing	1.0	D	0.834	deleterious	None	None	None	None	N
E/P	0.9955	likely_pathogenic	0.9961	pathogenic	-0.482	Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
E/Q	0.2629	likely_benign	0.2494	benign	-1.129	Destabilizing	1.0	D	0.753	deleterious	N	0.498944184	None	None	N
E/R	0.5814	likely_pathogenic	0.5578	ambiguous	-0.883	Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
E/S	0.4894	ambiguous	0.4518	ambiguous	-1.739	Destabilizing	0.999	D	0.753	deleterious	None	None	None	None	N
E/T	0.4949	ambiguous	0.4511	ambiguous	-1.42	Destabilizing	1.0	D	0.848	deleterious	None	None	None	None	N
E/V	0.3788	ambiguous	0.3466	ambiguous	-0.482	Destabilizing	1.0	D	0.867	deleterious	N	0.473875168	None	None	N
E/W	0.983	likely_pathogenic	0.98	pathogenic	-1.015	Destabilizing	1.0	D	0.852	deleterious	None	None	None	None	N
E/Y	0.9046	likely_pathogenic	0.8871	pathogenic	-0.84	Destabilizing	1.0	D	0.887	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.