TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26805	80638;80639;80640	chr2:178565719;178565718;178565717	chr2:179430446;179430445;179430444
N2AB	25164	75715;75716;75717	chr2:178565719;178565718;178565717	chr2:179430446;179430445;179430444
N2A	24237	72934;72935;72936	chr2:178565719;178565718;178565717	chr2:179430446;179430445;179430444
N2B	17740	53443;53444;53445	chr2:178565719;178565718;178565717	chr2:179430446;179430445;179430444
Novex-1	17865	53818;53819;53820	chr2:178565719;178565718;178565717	chr2:179430446;179430445;179430444
Novex-2	17932	54019;54020;54021	chr2:178565719;178565718;178565717	chr2:179430446;179430445;179430444
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: Fn3-83
• Domain position: 26
• Structural Position: 28
• Q(SASA): 0.9664
• 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	rs370095455	-0.033	0.064	N	0.411	0.223	None	gnomAD-2.1.1	2.5E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	4.71E-05	1.40568E-04
E/A	rs370095455	-0.033	0.064	N	0.411	0.223	None	gnomAD-3.1.2	1.32E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	2.94E-05	0	0
E/A	rs370095455	-0.033	0.064	N	0.411	0.223	None	gnomAD-4.0.0	4.58638E-05	None	None	None	None	N	None	1.33558E-05	0	None	0	0	None	0	0	6.01883E-05	0	3.20349E-05
E/Q	None	None	0.47	D	0.419	0.254	0.298056030225	gnomAD-4.0.0	6.00162E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	6.56252E-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	0.1663	likely_benign	0.1659	benign	-0.358	Destabilizing	0.064	N	0.411	neutral	N	0.47030364	None	None	N
E/C	0.8581	likely_pathogenic	0.8695	pathogenic	-0.006	Destabilizing	0.973	D	0.449	neutral	None	None	None	None	N
E/D	0.1231	likely_benign	0.1183	benign	-0.281	Destabilizing	None	N	0.113	neutral	N	0.488505398	None	None	N
E/F	0.7521	likely_pathogenic	0.7561	pathogenic	-0.364	Destabilizing	0.946	D	0.402	neutral	None	None	None	None	N
E/G	0.2389	likely_benign	0.2241	benign	-0.54	Destabilizing	0.003	N	0.269	neutral	N	0.474637695	None	None	N
E/H	0.5626	ambiguous	0.564	pathogenic	-0.161	Destabilizing	0.926	D	0.362	neutral	None	None	None	None	N
E/I	0.2478	likely_benign	0.2681	benign	0.081	Stabilizing	0.73	D	0.423	neutral	None	None	None	None	N
E/K	0.2137	likely_benign	0.2054	benign	0.19	Stabilizing	0.38	N	0.458	neutral	N	0.484694302	None	None	N
E/L	0.315	likely_benign	0.3207	benign	0.081	Stabilizing	0.73	D	0.414	neutral	None	None	None	None	N
E/M	0.4183	ambiguous	0.4249	ambiguous	0.188	Stabilizing	0.847	D	0.417	neutral	None	None	None	None	N
E/N	0.3079	likely_benign	0.3021	benign	0.066	Stabilizing	0.081	N	0.405	neutral	None	None	None	None	N
E/P	0.5431	ambiguous	0.5768	pathogenic	-0.045	Destabilizing	0.287	N	0.387	neutral	None	None	None	None	N
E/Q	0.1725	likely_benign	0.1735	benign	0.082	Stabilizing	0.47	N	0.419	neutral	D	0.522964689	None	None	N
E/R	0.3385	likely_benign	0.3413	ambiguous	0.378	Stabilizing	0.852	D	0.371	neutral	None	None	None	None	N
E/S	0.2183	likely_benign	0.2226	benign	-0.135	Destabilizing	0.305	N	0.406	neutral	None	None	None	None	N
E/T	0.2372	likely_benign	0.2455	benign	0.003	Stabilizing	0.377	N	0.428	neutral	None	None	None	None	N
E/V	0.1677	likely_benign	0.1823	benign	-0.045	Destabilizing	0.591	D	0.417	neutral	N	0.504725645	None	None	N
E/W	0.9041	likely_pathogenic	0.9072	pathogenic	-0.267	Destabilizing	0.994	D	0.516	neutral	None	None	None	None	N
E/Y	0.6644	likely_pathogenic	0.6593	pathogenic	-0.142	Destabilizing	0.979	D	0.415	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.