TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16620	50083;50084;50085	chr2:178612863;178612862;178612861	chr2:179477590;179477589;179477588
N2AB	14979	45160;45161;45162	chr2:178612863;178612862;178612861	chr2:179477590;179477589;179477588
N2A	14052	42379;42380;42381	chr2:178612863;178612862;178612861	chr2:179477590;179477589;179477588
N2B	7555	22888;22889;22890	chr2:178612863;178612862;178612861	chr2:179477590;179477589;179477588
Novex-1	7680	23263;23264;23265	chr2:178612863;178612862;178612861	chr2:179477590;179477589;179477588
Novex-2	7747	23464;23465;23466	chr2:178612863;178612862;178612861	chr2:179477590;179477589;179477588
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: Fn3-8
• Domain position: 70
• Structural Position: 103
• Q(SASA): 0.3527
• 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/D	None	None	0.434	N	0.208	0.128	0.246773566709	gnomAD-4.0.0	1.59388E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86208E-06	0	0
E/K	None	None	0.998	N	0.551	0.413	0.348983352498	gnomAD-4.0.0	4.10813E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	4.49923E-06	1.15977E-05	0
E/V	None	None	1.0	N	0.789	0.524	0.506006782367	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-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	0.317	likely_benign	0.383	ambiguous	-1.179	Destabilizing	0.998	D	0.656	neutral	N	0.514402056	None	None	N
E/C	0.9436	likely_pathogenic	0.9633	pathogenic	-0.625	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
E/D	0.4867	ambiguous	0.4764	ambiguous	-1.171	Destabilizing	0.434	N	0.208	neutral	N	0.505849972	None	None	N
E/F	0.9401	likely_pathogenic	0.9534	pathogenic	-0.611	Destabilizing	1.0	D	0.79	deleterious	None	None	None	None	N
E/G	0.4865	ambiguous	0.5867	pathogenic	-1.569	Destabilizing	0.999	D	0.742	deleterious	D	0.54460971	None	None	N
E/H	0.8439	likely_pathogenic	0.8878	pathogenic	-0.893	Destabilizing	1.0	D	0.708	prob.delet.	None	None	None	None	N
E/I	0.6243	likely_pathogenic	0.6763	pathogenic	-0.095	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
E/K	0.5018	ambiguous	0.6207	pathogenic	-0.912	Destabilizing	0.998	D	0.551	neutral	N	0.473706039	None	None	N
E/L	0.7006	likely_pathogenic	0.7499	pathogenic	-0.095	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
E/M	0.6827	likely_pathogenic	0.737	pathogenic	0.487	Stabilizing	1.0	D	0.763	deleterious	None	None	None	None	N
E/N	0.5959	likely_pathogenic	0.6421	pathogenic	-1.343	Destabilizing	0.999	D	0.719	prob.delet.	None	None	None	None	N
E/P	0.8068	likely_pathogenic	0.8423	pathogenic	-0.437	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
E/Q	0.3022	likely_benign	0.3705	ambiguous	-1.188	Destabilizing	0.999	D	0.655	neutral	N	0.483508037	None	None	N
E/R	0.6524	likely_pathogenic	0.7636	pathogenic	-0.65	Destabilizing	1.0	D	0.743	deleterious	None	None	None	None	N
E/S	0.4484	ambiguous	0.5117	ambiguous	-1.763	Destabilizing	0.997	D	0.593	neutral	None	None	None	None	N
E/T	0.4153	ambiguous	0.4727	ambiguous	-1.431	Destabilizing	1.0	D	0.76	deleterious	None	None	None	None	N
E/V	0.3942	ambiguous	0.4597	ambiguous	-0.437	Destabilizing	1.0	D	0.789	deleterious	N	0.478553306	None	None	N
E/W	0.9809	likely_pathogenic	0.9881	pathogenic	-0.347	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	N
E/Y	0.8929	likely_pathogenic	0.9202	pathogenic	-0.35	Destabilizing	1.0	D	0.79	deleterious	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.