TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16597	50014;50015;50016	chr2:178612932;178612931;178612930	chr2:179477659;179477658;179477657
N2AB	14956	45091;45092;45093	chr2:178612932;178612931;178612930	chr2:179477659;179477658;179477657
N2A	14029	42310;42311;42312	chr2:178612932;178612931;178612930	chr2:179477659;179477658;179477657
N2B	7532	22819;22820;22821	chr2:178612932;178612931;178612930	chr2:179477659;179477658;179477657
Novex-1	7657	23194;23195;23196	chr2:178612932;178612931;178612930	chr2:179477659;179477658;179477657
Novex-2	7724	23395;23396;23397	chr2:178612932;178612931;178612930	chr2:179477659;179477658;179477657
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: Fn3-8
• Domain position: 47
• Structural Position: 64
• Q(SASA): 0.5406
• 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/D	None	None	None	N	0.237	0.048	0.0986583533028	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-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	0.1674	likely_benign	0.2258	benign	-0.177	Destabilizing	0.22	N	0.431	neutral	N	0.48452877	None	None	I
E/C	0.7863	likely_pathogenic	0.8575	pathogenic	-0.26	Destabilizing	0.968	D	0.633	neutral	None	None	None	None	I
E/D	0.0616	likely_benign	0.0704	benign	-0.279	Destabilizing	None	N	0.237	neutral	N	0.451731425	None	None	I
E/F	0.7393	likely_pathogenic	0.8197	pathogenic	-0.078	Destabilizing	0.89	D	0.566	neutral	None	None	None	None	I
E/G	0.2093	likely_benign	0.294	benign	-0.336	Destabilizing	0.22	N	0.453	neutral	N	0.479381702	None	None	I
E/H	0.4228	ambiguous	0.5619	ambiguous	0.46	Stabilizing	0.726	D	0.415	neutral	None	None	None	None	I
E/I	0.369	ambiguous	0.448	ambiguous	0.197	Stabilizing	0.726	D	0.563	neutral	None	None	None	None	I
E/K	0.181	likely_benign	0.2662	benign	0.291	Stabilizing	0.22	N	0.427	neutral	N	0.469920777	None	None	I
E/L	0.4276	ambiguous	0.5268	ambiguous	0.197	Stabilizing	0.567	D	0.558	neutral	None	None	None	None	I
E/M	0.5093	ambiguous	0.5807	pathogenic	0.002	Stabilizing	0.968	D	0.544	neutral	None	None	None	None	I
E/N	0.1412	likely_benign	0.188	benign	-0.005	Destabilizing	0.157	N	0.415	neutral	None	None	None	None	I
E/P	0.832	likely_pathogenic	0.9019	pathogenic	0.091	Stabilizing	0.726	D	0.428	neutral	None	None	None	None	I
E/Q	0.1681	likely_benign	0.2146	benign	0.027	Stabilizing	0.22	N	0.383	neutral	N	0.483649419	None	None	I
E/R	0.3012	likely_benign	0.4431	ambiguous	0.603	Stabilizing	0.567	D	0.414	neutral	None	None	None	None	I
E/S	0.1517	likely_benign	0.1999	benign	-0.167	Destabilizing	0.157	N	0.429	neutral	None	None	None	None	I
E/T	0.1931	likely_benign	0.2483	benign	-0.032	Destabilizing	0.272	N	0.393	neutral	None	None	None	None	I
E/V	0.2329	likely_benign	0.2971	benign	0.091	Stabilizing	0.667	D	0.481	neutral	N	0.481420516	None	None	I
E/W	0.9135	likely_pathogenic	0.9536	pathogenic	0.029	Stabilizing	0.968	D	0.653	neutral	None	None	None	None	I
E/Y	0.5498	ambiguous	0.684	pathogenic	0.155	Stabilizing	0.89	D	0.515	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.