TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8048	24367;24368;24369	chr2:178719248;178719247;178719246	chr2:179583975;179583974;179583973
N2AB	7731	23416;23417;23418	chr2:178719248;178719247;178719246	chr2:179583975;179583974;179583973
N2A	6804	20635;20636;20637	chr2:178719248;178719247;178719246	chr2:179583975;179583974;179583973
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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-65
• Domain position: 64
• Structural Position: 145
• Q(SASA): 0.4109
• Predicted PPI site: I

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	None	None	0.012	N	0.203	0.202	0.401612077098	gnomAD-4.0.0	1.59128E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85842E-06	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	0.1213	likely_benign	0.1262	benign	-0.542	Destabilizing	0.454	N	0.33	neutral	N	0.50827853	None	None	I
E/C	0.7177	likely_pathogenic	0.7261	pathogenic	-0.212	Destabilizing	0.998	D	0.491	neutral	None	None	None	None	I
E/D	0.1021	likely_benign	0.099	benign	-0.535	Destabilizing	0.012	N	0.146	neutral	N	0.451886529	None	None	I
E/F	0.5426	ambiguous	0.5629	ambiguous	-0.076	Destabilizing	0.991	D	0.435	neutral	None	None	None	None	I
E/G	0.0933	likely_benign	0.0963	benign	-0.826	Destabilizing	0.012	N	0.203	neutral	N	0.483556231	None	None	I
E/H	0.2561	likely_benign	0.2795	benign	0.004	Stabilizing	0.991	D	0.371	neutral	None	None	None	None	I
E/I	0.2647	likely_benign	0.2815	benign	0.205	Stabilizing	0.974	D	0.445	neutral	None	None	None	None	I
E/K	0.0871	likely_benign	0.0996	benign	0.1	Stabilizing	0.022	N	0.111	neutral	N	0.463428888	None	None	I
E/L	0.2071	likely_benign	0.2203	benign	0.205	Stabilizing	0.915	D	0.405	neutral	None	None	None	None	I
E/M	0.3089	likely_benign	0.3181	benign	0.372	Stabilizing	0.998	D	0.411	neutral	None	None	None	None	I
E/N	0.1625	likely_benign	0.1662	benign	-0.452	Destabilizing	0.728	D	0.269	neutral	None	None	None	None	I
E/P	0.6351	likely_pathogenic	0.6589	pathogenic	-0.022	Destabilizing	0.974	D	0.375	neutral	None	None	None	None	I
E/Q	0.0828	likely_benign	0.09	benign	-0.337	Destabilizing	0.801	D	0.382	neutral	N	0.431183183	None	None	I
E/R	0.1503	likely_benign	0.1669	benign	0.384	Stabilizing	0.728	D	0.333	neutral	None	None	None	None	I
E/S	0.1284	likely_benign	0.1316	benign	-0.636	Destabilizing	0.842	D	0.248	neutral	None	None	None	None	I
E/T	0.1661	likely_benign	0.1764	benign	-0.39	Destabilizing	0.842	D	0.363	neutral	None	None	None	None	I
E/V	0.1551	likely_benign	0.1616	benign	-0.022	Destabilizing	0.891	D	0.385	neutral	N	0.501411273	None	None	I
E/W	0.7782	likely_pathogenic	0.7921	pathogenic	0.18	Stabilizing	0.998	D	0.564	neutral	None	None	None	None	I
E/Y	0.4106	ambiguous	0.4316	ambiguous	0.19	Stabilizing	0.991	D	0.421	neutral	None	None	None	None	I

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.