TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29448	88567;88568;88569	chr2:178555117;178555116;178555115	chr2:179419844;179419843;179419842
N2AB	27807	83644;83645;83646	chr2:178555117;178555116;178555115	chr2:179419844;179419843;179419842
N2A	26880	80863;80864;80865	chr2:178555117;178555116;178555115	chr2:179419844;179419843;179419842
N2B	20383	61372;61373;61374	chr2:178555117;178555116;178555115	chr2:179419844;179419843;179419842
Novex-1	20508	61747;61748;61749	chr2:178555117;178555116;178555115	chr2:179419844;179419843;179419842
Novex-2	20575	61948;61949;61950	chr2:178555117;178555116;178555115	chr2:179419844;179419843;179419842
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: Ig-146
• Domain position: 5
• Structural Position: 9
• Q(SASA): 0.8468
• 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/Q	None	None	0.891	N	0.377	0.182	0.211220785272	gnomAD-4.0.0	1.59247E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85886E-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	0.2112	likely_benign	0.1699	benign	-0.122	Destabilizing	0.454	N	0.418	neutral	N	0.476277102	None	None	I
E/C	0.9077	likely_pathogenic	0.8771	pathogenic	0.025	Stabilizing	0.998	D	0.365	neutral	None	None	None	None	I
E/D	0.0893	likely_benign	0.0829	benign	-0.239	Destabilizing	0.005	N	0.231	neutral	N	0.448821142	None	None	I
E/F	0.9171	likely_pathogenic	0.8778	pathogenic	-0.095	Destabilizing	0.991	D	0.375	neutral	None	None	None	None	I
E/G	0.194	likely_benign	0.1565	benign	-0.281	Destabilizing	0.625	D	0.393	neutral	N	0.480317485	None	None	I
E/H	0.5344	ambiguous	0.4667	ambiguous	0.287	Stabilizing	0.974	D	0.389	neutral	None	None	None	None	I
E/I	0.7248	likely_pathogenic	0.6395	pathogenic	0.246	Stabilizing	0.974	D	0.383	neutral	None	None	None	None	I
E/K	0.2149	likely_benign	0.1644	benign	0.528	Stabilizing	0.801	D	0.395	neutral	N	0.464153167	None	None	I
E/L	0.6834	likely_pathogenic	0.5936	pathogenic	0.246	Stabilizing	0.915	D	0.374	neutral	None	None	None	None	I
E/M	0.6917	likely_pathogenic	0.6085	pathogenic	0.189	Stabilizing	0.998	D	0.363	neutral	None	None	None	None	I
E/N	0.2279	likely_benign	0.1875	benign	0.239	Stabilizing	0.067	N	0.278	neutral	None	None	None	None	I
E/P	0.8101	likely_pathogenic	0.7615	pathogenic	0.143	Stabilizing	0.974	D	0.355	neutral	None	None	None	None	I
E/Q	0.1994	likely_benign	0.1673	benign	0.264	Stabilizing	0.891	D	0.377	neutral	N	0.442836532	None	None	I
E/R	0.359	ambiguous	0.2899	benign	0.703	Stabilizing	0.974	D	0.367	neutral	None	None	None	None	I
E/S	0.217	likely_benign	0.176	benign	0.099	Stabilizing	0.08	N	0.23	neutral	None	None	None	None	I
E/T	0.2932	likely_benign	0.2349	benign	0.233	Stabilizing	0.728	D	0.405	neutral	None	None	None	None	I
E/V	0.4471	ambiguous	0.3718	ambiguous	0.143	Stabilizing	0.891	D	0.383	neutral	N	0.491707914	None	None	I
E/W	0.9566	likely_pathogenic	0.934	pathogenic	-0.004	Destabilizing	0.998	D	0.449	neutral	None	None	None	None	I
E/Y	0.7994	likely_pathogenic	0.7317	pathogenic	0.145	Stabilizing	0.991	D	0.379	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.