TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17217	51874;51875;51876	chr2:178609774;178609773;178609772	chr2:179474501;179474500;179474499
N2AB	15576	46951;46952;46953	chr2:178609774;178609773;178609772	chr2:179474501;179474500;179474499
N2A	14649	44170;44171;44172	chr2:178609774;178609773;178609772	chr2:179474501;179474500;179474499
N2B	8152	24679;24680;24681	chr2:178609774;178609773;178609772	chr2:179474501;179474500;179474499
Novex-1	8277	25054;25055;25056	chr2:178609774;178609773;178609772	chr2:179474501;179474500;179474499
Novex-2	8344	25255;25256;25257	chr2:178609774;178609773;178609772	chr2:179474501;179474500;179474499
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: Fn3-13
• Domain position: 71
• Structural Position: 103
• Q(SASA): 0.3797
• 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	0.704	N	0.376	0.21	0.379020345274	gnomAD-4.0.0	6.84539E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	1.65777E-05
E/D	None	None	0.704	N	0.357	0.11	0.229924730088	gnomAD-4.0.0	1.36909E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79971E-06	0	0
E/G	None	None	0.826	N	0.43	0.274	0.428630128466	gnomAD-4.0.0	6.84539E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99849E-07	0	0
E/K	rs1060500503	-0.732	0.704	N	0.39	0.223	0.311079019809	gnomAD-2.1.1	8.05E-06	None	None	None	None	N	None	1.294E-04	0	None	0	0	None	0	None	0	0	0
E/K	rs1060500503	-0.732	0.704	N	0.39	0.223	0.311079019809	gnomAD-4.0.0	3.42267E-06	None	None	None	None	N	None	2.9933E-05	0	None	0	0	None	0	1.73792E-04	8.99849E-07	1.16009E-05	1.65772E-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	0.2953	likely_benign	0.2951	benign	-0.976	Destabilizing	0.704	D	0.376	neutral	N	0.508496668	None	None	N
E/C	0.9265	likely_pathogenic	0.9202	pathogenic	-0.473	Destabilizing	0.999	D	0.573	neutral	None	None	None	None	N
E/D	0.3415	ambiguous	0.3184	benign	-1.014	Destabilizing	0.704	D	0.357	neutral	N	0.507341875	None	None	N
E/F	0.8706	likely_pathogenic	0.8506	pathogenic	-0.291	Destabilizing	0.997	D	0.554	neutral	None	None	None	None	N
E/G	0.5146	ambiguous	0.498	ambiguous	-1.361	Destabilizing	0.826	D	0.43	neutral	N	0.476296763	None	None	N
E/H	0.8107	likely_pathogenic	0.792	pathogenic	-0.535	Destabilizing	0.991	D	0.465	neutral	None	None	None	None	N
E/I	0.4672	ambiguous	0.4559	ambiguous	0.085	Stabilizing	0.991	D	0.56	neutral	None	None	None	None	N
E/K	0.6046	likely_pathogenic	0.5775	pathogenic	-0.568	Destabilizing	0.704	D	0.39	neutral	N	0.459972003	None	None	N
E/L	0.5988	likely_pathogenic	0.5803	pathogenic	0.085	Stabilizing	0.939	D	0.533	neutral	None	None	None	None	N
E/M	0.5655	likely_pathogenic	0.5548	ambiguous	0.549	Stabilizing	0.999	D	0.541	neutral	None	None	None	None	N
E/N	0.5788	likely_pathogenic	0.5656	pathogenic	-1.101	Destabilizing	0.17	N	0.291	neutral	None	None	None	None	N
E/P	0.8217	likely_pathogenic	0.8454	pathogenic	-0.248	Destabilizing	0.046	N	0.33	neutral	None	None	None	None	N
E/Q	0.3016	likely_benign	0.2991	benign	-0.95	Destabilizing	0.31	N	0.187	neutral	N	0.45743313	None	None	N
E/R	0.728	likely_pathogenic	0.7062	pathogenic	-0.285	Destabilizing	0.939	D	0.428	neutral	None	None	None	None	N
E/S	0.4154	ambiguous	0.4082	ambiguous	-1.451	Destabilizing	0.373	N	0.149	neutral	None	None	None	None	N
E/T	0.361	ambiguous	0.3522	ambiguous	-1.121	Destabilizing	0.884	D	0.382	neutral	None	None	None	None	N
E/V	0.2926	likely_benign	0.2814	benign	-0.248	Destabilizing	0.959	D	0.521	neutral	N	0.507573949	None	None	N
E/W	0.9441	likely_pathogenic	0.9282	pathogenic	0.026	Stabilizing	0.999	D	0.616	neutral	None	None	None	None	N
E/Y	0.795	likely_pathogenic	0.7502	pathogenic	-0.008	Destabilizing	0.997	D	0.56	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.