TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22733	68422;68423;68424	chr2:178578833;178578832;178578831	chr2:179443560;179443559;179443558
N2AB	21092	63499;63500;63501	chr2:178578833;178578832;178578831	chr2:179443560;179443559;179443558
N2A	20165	60718;60719;60720	chr2:178578833;178578832;178578831	chr2:179443560;179443559;179443558
N2B	13668	41227;41228;41229	chr2:178578833;178578832;178578831	chr2:179443560;179443559;179443558
Novex-1	13793	41602;41603;41604	chr2:178578833;178578832;178578831	chr2:179443560;179443559;179443558
Novex-2	13860	41803;41804;41805	chr2:178578833;178578832;178578831	chr2:179443560;179443559;179443558
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: Fn3-52
• Domain position: 91
• Structural Position: 124
• Q(SASA): 0.798
• 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	rs754767867	0.089	0.03	N	0.458	0.246	0.230578612272	gnomAD-2.1.1	1.79E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	3.14E-05	1.41163E-04
E/A	rs754767867	0.089	0.03	N	0.458	0.246	0.230578612272	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
E/A	rs754767867	0.089	0.03	N	0.458	0.246	0.230578612272	gnomAD-4.0.0	1.24118E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.69725E-05	0	0
E/G	rs754767867	-0.144	0.058	N	0.547	0.228	0.269111216191	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.31E-05	None	0	0	0
E/G	rs754767867	-0.144	0.058	N	0.547	0.228	0.269111216191	gnomAD-4.0.0	6.85239E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.16439E-05	0
E/Q	None	None	0.058	N	0.582	0.132	0.187945064343	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	6.33473E-05	0	None	0	0	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	0.1024	likely_benign	0.1	benign	-0.146	Destabilizing	0.03	N	0.458	neutral	N	0.521748393	None	None	N
E/C	0.6851	likely_pathogenic	0.691	pathogenic	-0.188	Destabilizing	0.869	D	0.588	neutral	None	None	None	None	N
E/D	0.0718	likely_benign	0.0712	benign	-0.309	Destabilizing	None	N	0.133	neutral	N	0.466972546	None	None	N
E/F	0.5948	likely_pathogenic	0.5878	pathogenic	-0.026	Destabilizing	0.366	N	0.58	neutral	None	None	None	None	N
E/G	0.1106	likely_benign	0.1157	benign	-0.303	Destabilizing	0.058	N	0.547	neutral	N	0.476102045	None	None	N
E/H	0.3389	likely_benign	0.3451	ambiguous	0.525	Stabilizing	0.366	N	0.491	neutral	None	None	None	None	N
E/I	0.2324	likely_benign	0.2239	benign	0.222	Stabilizing	0.221	N	0.609	neutral	None	None	None	None	N
E/K	0.1005	likely_benign	0.1014	benign	0.435	Stabilizing	0.058	N	0.513	neutral	N	0.497295453	None	None	N
E/L	0.2358	likely_benign	0.226	benign	0.222	Stabilizing	0.039	N	0.608	neutral	None	None	None	None	N
E/M	0.3209	likely_benign	0.2973	benign	0.056	Stabilizing	0.869	D	0.58	neutral	None	None	None	None	N
E/N	0.1437	likely_benign	0.1411	benign	0.039	Stabilizing	0.039	N	0.431	neutral	None	None	None	None	N
E/P	0.2402	likely_benign	0.2373	benign	0.118	Stabilizing	0.366	N	0.565	neutral	None	None	None	None	N
E/Q	0.109	likely_benign	0.1095	benign	0.08	Stabilizing	0.058	N	0.582	neutral	N	0.519190878	None	None	N
E/R	0.1928	likely_benign	0.1953	benign	0.72	Stabilizing	0.221	N	0.527	neutral	None	None	None	None	N
E/S	0.1247	likely_benign	0.1231	benign	-0.086	Destabilizing	0.039	N	0.416	neutral	None	None	None	None	N
E/T	0.1481	likely_benign	0.1426	benign	0.054	Stabilizing	None	N	0.365	neutral	None	None	None	None	N
E/V	0.1491	likely_benign	0.1406	benign	0.118	Stabilizing	0.03	N	0.578	neutral	N	0.483988857	None	None	N
E/W	0.8223	likely_pathogenic	0.8263	pathogenic	0.091	Stabilizing	0.869	D	0.647	neutral	None	None	None	None	N
E/Y	0.4422	ambiguous	0.4459	ambiguous	0.216	Stabilizing	0.637	D	0.595	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.