TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26558	79897;79898;79899	chr2:178566460;178566459;178566458	chr2:179431187;179431186;179431185
N2AB	24917	74974;74975;74976	chr2:178566460;178566459;178566458	chr2:179431187;179431186;179431185
N2A	23990	72193;72194;72195	chr2:178566460;178566459;178566458	chr2:179431187;179431186;179431185
N2B	17493	52702;52703;52704	chr2:178566460;178566459;178566458	chr2:179431187;179431186;179431185
Novex-1	17618	53077;53078;53079	chr2:178566460;178566459;178566458	chr2:179431187;179431186;179431185
Novex-2	17685	53278;53279;53280	chr2:178566460;178566459;178566458	chr2:179431187;179431186;179431185
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: Fn3-81
• Domain position: 72
• Structural Position: 103
• Q(SASA): 0.3076
• 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/A	None	None	0.805	N	0.531	0.372	0.395894371353	gnomAD-4.0.0	2.73734E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.59808E-06	0	0
E/K	rs1466993099	-1.111	0.805	N	0.501	0.293	0.319970858106	gnomAD-2.1.1	8.05E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.78E-05	0
E/K	rs1466993099	-1.111	0.805	N	0.501	0.293	0.319970858106	gnomAD-4.0.0	2.73741E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.59807E-06	0	0
E/Q	None	None	0.204	N	0.263	0.187	0.190952846119	gnomAD-4.0.0	2.73741E-06	None	None	None	None	N	None	2.989E-05	0	None	0	0	None	1.88034E-05	0	8.99518E-07	1.15937E-05	0
E/V	rs1026820295	None	0.935	N	0.68	0.426	0.568143352941	gnomAD-4.0.0	1.36867E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.31389E-05

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	0.126	likely_benign	0.1319	benign	-1.02	Destabilizing	0.805	D	0.531	neutral	N	0.486069679	None	None	N
E/C	0.807	likely_pathogenic	0.823	pathogenic	-0.591	Destabilizing	0.999	D	0.759	deleterious	None	None	None	None	N
E/D	0.1836	likely_benign	0.1862	benign	-1.365	Destabilizing	0.892	D	0.464	neutral	N	0.4855627	None	None	N
E/F	0.751	likely_pathogenic	0.7773	pathogenic	-0.566	Destabilizing	0.987	D	0.776	deleterious	None	None	None	None	N
E/G	0.1995	likely_benign	0.2033	benign	-1.411	Destabilizing	0.892	D	0.654	neutral	N	0.490450999	None	None	N
E/H	0.5259	ambiguous	0.585	pathogenic	-0.902	Destabilizing	0.997	D	0.627	neutral	None	None	None	None	N
E/I	0.2944	likely_benign	0.3108	benign	0.057	Stabilizing	0.975	D	0.792	deleterious	None	None	None	None	N
E/K	0.2057	likely_benign	0.2372	benign	-0.977	Destabilizing	0.805	D	0.501	neutral	N	0.493103142	None	None	N
E/L	0.342	ambiguous	0.3755	ambiguous	0.057	Stabilizing	0.95	D	0.716	prob.delet.	None	None	None	None	N
E/M	0.3814	ambiguous	0.4101	ambiguous	0.643	Stabilizing	0.999	D	0.74	deleterious	None	None	None	None	N
E/N	0.2751	likely_benign	0.2919	benign	-1.381	Destabilizing	0.975	D	0.604	neutral	None	None	None	None	N
E/P	0.3743	ambiguous	0.4127	ambiguous	-0.281	Destabilizing	0.987	D	0.745	deleterious	None	None	None	None	N
E/Q	0.146	likely_benign	0.1675	benign	-1.225	Destabilizing	0.204	N	0.263	neutral	N	0.510766183	None	None	N
E/R	0.3676	ambiguous	0.4151	ambiguous	-0.724	Destabilizing	0.95	D	0.614	neutral	None	None	None	None	N
E/S	0.2223	likely_benign	0.2346	benign	-1.784	Destabilizing	0.845	D	0.489	neutral	None	None	None	None	N
E/T	0.1986	likely_benign	0.2109	benign	-1.459	Destabilizing	0.073	N	0.315	neutral	None	None	None	None	N
E/V	0.1779	likely_benign	0.1875	benign	-0.281	Destabilizing	0.935	D	0.68	prob.neutral	N	0.484944044	None	None	N
E/W	0.9096	likely_pathogenic	0.9272	pathogenic	-0.39	Destabilizing	0.999	D	0.737	prob.delet.	None	None	None	None	N
E/Y	0.6321	likely_pathogenic	0.6751	pathogenic	-0.335	Destabilizing	0.996	D	0.767	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.