TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15395	46408;46409;46410	chr2:178620338;178620337;178620336	chr2:179485065;179485064;179485063
N2AB	13754	41485;41486;41487	chr2:178620338;178620337;178620336	chr2:179485065;179485064;179485063
N2A	12827	38704;38705;38706	chr2:178620338;178620337;178620336	chr2:179485065;179485064;179485063
N2B	6330	19213;19214;19215	chr2:178620338;178620337;178620336	chr2:179485065;179485064;179485063
Novex-1	6455	19588;19589;19590	chr2:178620338;178620337;178620336	chr2:179485065;179485064;179485063
Novex-2	6522	19789;19790;19791	chr2:178620338;178620337;178620336	chr2:179485065;179485064;179485063
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: Ig-106
• Domain position: 5
• Structural Position: 5
• Q(SASA): 0.2447
• 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	None	None	0.669	N	0.483	0.208	0.36036328697	gnomAD-4.0.0	6.91192E-07	None	None	None	None	N	None	3.02828E-05	0	None	0	0	None	0	0	0	0	0
E/K	rs771991019	-0.9	0.669	N	0.424	0.247	0.271763555656	gnomAD-2.1.1	4.18E-06	None	None	None	None	N	None	0	0	None	0	5.62E-05	None	0	None	0	0	0
E/K	rs771991019	-0.9	0.669	N	0.424	0.247	0.271763555656	gnomAD-4.0.0	4.1461E-06	None	None	None	None	N	None	0	0	None	0	7.60109E-05	None	0	0	0	2.38624E-05	1.67532E-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	0.1612	likely_benign	0.2089	benign	-0.789	Destabilizing	0.022	N	0.195	neutral	N	0.431875973	None	None	N
E/C	0.8236	likely_pathogenic	0.8907	pathogenic	-0.406	Destabilizing	0.998	D	0.568	neutral	None	None	None	None	N
E/D	0.1937	likely_benign	0.2782	benign	-0.758	Destabilizing	0.801	D	0.409	neutral	N	0.501573347	None	None	N
E/F	0.7795	likely_pathogenic	0.8387	pathogenic	-0.396	Destabilizing	0.974	D	0.594	neutral	None	None	None	None	N
E/G	0.2129	likely_benign	0.2661	benign	-1.083	Destabilizing	0.669	D	0.483	neutral	N	0.489136921	None	None	N
E/H	0.3964	ambiguous	0.5063	ambiguous	-0.475	Destabilizing	0.974	D	0.469	neutral	None	None	None	None	N
E/I	0.4735	ambiguous	0.5668	pathogenic	-0.01	Destabilizing	0.728	D	0.551	neutral	None	None	None	None	N
E/K	0.1461	likely_benign	0.1818	benign	-0.468	Destabilizing	0.669	D	0.424	neutral	N	0.394942615	None	None	N
E/L	0.4771	ambiguous	0.5636	ambiguous	-0.01	Destabilizing	0.728	D	0.507	neutral	None	None	None	None	N
E/M	0.5376	ambiguous	0.6243	pathogenic	0.298	Stabilizing	0.974	D	0.566	neutral	None	None	None	None	N
E/N	0.2784	likely_benign	0.4149	ambiguous	-0.789	Destabilizing	0.949	D	0.451	neutral	None	None	None	None	N
E/P	0.917	likely_pathogenic	0.9655	pathogenic	-0.249	Destabilizing	0.974	D	0.517	neutral	None	None	None	None	N
E/Q	0.1132	likely_benign	0.1417	benign	-0.706	Destabilizing	0.051	N	0.225	neutral	N	0.425439426	None	None	N
E/R	0.2154	likely_benign	0.2473	benign	-0.141	Destabilizing	0.728	D	0.435	neutral	None	None	None	None	N
E/S	0.1796	likely_benign	0.2368	benign	-1.052	Destabilizing	0.525	D	0.391	neutral	None	None	None	None	N
E/T	0.203	likely_benign	0.2765	benign	-0.82	Destabilizing	0.842	D	0.459	neutral	None	None	None	None	N
E/V	0.2932	likely_benign	0.3591	ambiguous	-0.249	Destabilizing	0.051	N	0.309	neutral	N	0.445187935	None	None	N
E/W	0.9115	likely_pathogenic	0.9432	pathogenic	-0.167	Destabilizing	0.998	D	0.594	neutral	None	None	None	None	N
E/Y	0.6798	likely_pathogenic	0.754	pathogenic	-0.168	Destabilizing	0.991	D	0.581	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.