TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24212	72859;72860;72861	chr2:178573498;178573497;178573496	chr2:179438225;179438224;179438223
N2AB	22571	67936;67937;67938	chr2:178573498;178573497;178573496	chr2:179438225;179438224;179438223
N2A	21644	65155;65156;65157	chr2:178573498;178573497;178573496	chr2:179438225;179438224;179438223
N2B	15147	45664;45665;45666	chr2:178573498;178573497;178573496	chr2:179438225;179438224;179438223
Novex-1	15272	46039;46040;46041	chr2:178573498;178573497;178573496	chr2:179438225;179438224;179438223
Novex-2	15339	46240;46241;46242	chr2:178573498;178573497;178573496	chr2:179438225;179438224;179438223
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: Fn3-63
• Domain position: 91
• Structural Position: 125
• Q(SASA): 0.8405
• 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/G	rs1708983044	None	0.501	N	0.578	0.27	0.308904156042	gnomAD-4.0.0	5.8205E-06	None	None	None	None	N	None	0	0	None	0	8.71283E-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	0.0973	likely_benign	0.1026	benign	-0.103	Destabilizing	0.172	N	0.445	neutral	D	0.522017752	None	None	N
E/C	0.6223	likely_pathogenic	0.6922	pathogenic	-0.25	Destabilizing	0.991	D	0.539	neutral	None	None	None	None	N
E/D	0.0737	likely_benign	0.0805	benign	-0.317	Destabilizing	0.001	N	0.167	neutral	N	0.479363053	None	None	N
E/F	0.5114	ambiguous	0.5797	pathogenic	-0.052	Destabilizing	0.824	D	0.548	neutral	None	None	None	None	N
E/G	0.0994	likely_benign	0.11	benign	-0.239	Destabilizing	0.501	D	0.578	neutral	N	0.490585449	None	None	N
E/H	0.2816	likely_benign	0.3275	benign	0.56	Stabilizing	0.905	D	0.487	neutral	None	None	None	None	N
E/I	0.1895	likely_benign	0.2099	benign	0.204	Stabilizing	0.01	N	0.352	neutral	None	None	None	None	N
E/K	0.0815	likely_benign	0.0917	benign	0.375	Stabilizing	0.335	N	0.455	neutral	N	0.47722768	None	None	N
E/L	0.2007	likely_benign	0.2275	benign	0.204	Stabilizing	0.187	N	0.539	neutral	None	None	None	None	N
E/M	0.2626	likely_benign	0.2917	benign	-0.014	Destabilizing	0.824	D	0.545	neutral	None	None	None	None	N
E/N	0.1406	likely_benign	0.1608	benign	0.046	Stabilizing	0.824	D	0.505	neutral	None	None	None	None	N
E/P	0.2401	likely_benign	0.2692	benign	0.12	Stabilizing	0.905	D	0.593	neutral	None	None	None	None	N
E/Q	0.0964	likely_benign	0.1043	benign	0.074	Stabilizing	0.03	N	0.31	neutral	N	0.486457619	None	None	N
E/R	0.1559	likely_benign	0.1772	benign	0.662	Stabilizing	0.7	D	0.523	neutral	None	None	None	None	N
E/S	0.1135	likely_benign	0.1246	benign	-0.088	Destabilizing	0.4	N	0.441	neutral	None	None	None	None	N
E/T	0.1339	likely_benign	0.1481	benign	0.033	Stabilizing	0.571	D	0.524	neutral	None	None	None	None	N
E/V	0.1201	likely_benign	0.1293	benign	0.12	Stabilizing	0.003	N	0.367	neutral	N	0.49007847	None	None	N
E/W	0.7483	likely_pathogenic	0.8112	pathogenic	0.033	Stabilizing	0.991	D	0.603	neutral	None	None	None	None	N
E/Y	0.3815	ambiguous	0.4397	ambiguous	0.179	Stabilizing	0.905	D	0.562	neutral	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.