TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19659	59200;59201;59202	chr2:178593233;178593232;178593231	chr2:179457960;179457959;179457958
N2AB	18018	54277;54278;54279	chr2:178593233;178593232;178593231	chr2:179457960;179457959;179457958
N2A	17091	51496;51497;51498	chr2:178593233;178593232;178593231	chr2:179457960;179457959;179457958
N2B	10594	32005;32006;32007	chr2:178593233;178593232;178593231	chr2:179457960;179457959;179457958
Novex-1	10719	32380;32381;32382	chr2:178593233;178593232;178593231	chr2:179457960;179457959;179457958
Novex-2	10786	32581;32582;32583	chr2:178593233;178593232;178593231	chr2:179457960;179457959;179457958
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: Fn3-30
• Domain position: 81
• Structural Position: 113
• Q(SASA): 0.495
• 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/D	None	None	0.722	N	0.417	0.099	0.368554958709	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
E/K	rs2050629562	None	0.565	N	0.443	0.257	0.260249123532	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
E/K	rs2050629562	None	0.565	N	0.443	0.257	0.260249123532	gnomAD-4.0.0	7.10514E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.43487E-06	0	0
E/Q	None	None	0.075	N	0.235	0.111	0.301789629655	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-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	0.1768	likely_benign	0.1767	benign	-0.464	Destabilizing	0.565	D	0.494	neutral	N	0.439095298	None	None	I
E/C	0.8798	likely_pathogenic	0.8776	pathogenic	-0.101	Destabilizing	0.996	D	0.625	neutral	None	None	None	None	I
E/D	0.1771	likely_benign	0.17	benign	-0.486	Destabilizing	0.722	D	0.417	neutral	N	0.486926531	None	None	I
E/F	0.8664	likely_pathogenic	0.865	pathogenic	-0.271	Destabilizing	0.961	D	0.602	neutral	None	None	None	None	I
E/G	0.2768	likely_benign	0.2667	benign	-0.692	Destabilizing	0.722	D	0.558	neutral	N	0.505757434	None	None	I
E/H	0.6339	likely_pathogenic	0.619	pathogenic	-0.134	Destabilizing	0.989	D	0.369	neutral	None	None	None	None	I
E/I	0.3585	ambiguous	0.3458	ambiguous	0.114	Stabilizing	0.096	N	0.475	neutral	None	None	None	None	I
E/K	0.2664	likely_benign	0.2491	benign	0.187	Stabilizing	0.565	D	0.443	neutral	N	0.457662416	None	None	I
E/L	0.5504	ambiguous	0.5293	ambiguous	0.114	Stabilizing	0.633	D	0.564	neutral	None	None	None	None	I
E/M	0.5459	ambiguous	0.5236	ambiguous	0.254	Stabilizing	0.961	D	0.59	neutral	None	None	None	None	I
E/N	0.414	ambiguous	0.4005	ambiguous	-0.19	Destabilizing	0.923	D	0.393	neutral	None	None	None	None	I
E/P	0.7396	likely_pathogenic	0.7513	pathogenic	-0.057	Destabilizing	0.961	D	0.506	neutral	None	None	None	None	I
E/Q	0.2164	likely_benign	0.2106	benign	-0.131	Destabilizing	0.075	N	0.235	neutral	N	0.504877573	None	None	I
E/R	0.4156	ambiguous	0.4087	ambiguous	0.405	Stabilizing	0.858	D	0.389	neutral	None	None	None	None	I
E/S	0.2753	likely_benign	0.2751	benign	-0.349	Destabilizing	0.633	D	0.433	neutral	None	None	None	None	I
E/T	0.3123	likely_benign	0.3036	benign	-0.161	Destabilizing	0.775	D	0.539	neutral	None	None	None	None	I
E/V	0.2489	likely_benign	0.2361	benign	-0.057	Destabilizing	0.034	N	0.411	neutral	N	0.482867505	None	None	I
E/W	0.9519	likely_pathogenic	0.9536	pathogenic	-0.096	Destabilizing	0.996	D	0.683	prob.neutral	None	None	None	None	I
E/Y	0.7682	likely_pathogenic	0.7734	pathogenic	-0.025	Destabilizing	0.961	D	0.593	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.