TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5345	16258;16259;16260	chr2:178733260;178733259;178733258	chr2:179597987;179597986;179597985
N2AB	5028	15307;15308;15309	chr2:178733260;178733259;178733258	chr2:179597987;179597986;179597985
N2A	4101	12526;12527;12528	chr2:178733260;178733259;178733258	chr2:179597987;179597986;179597985
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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: Ig-36
• Domain position: 85
• Structural Position: 171
• Q(SASA): 0.5404
• 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	rs1298041878	-0.231	0.425	N	0.335	0.095	0.282575091529	gnomAD-2.1.1	3.18E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	6.48E-05	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	0.1359	likely_benign	0.1556	benign	-0.238	Destabilizing	0.139	N	0.271	neutral	N	0.439437307	None	None	N
E/C	0.789	likely_pathogenic	0.8336	pathogenic	0.263	Stabilizing	0.981	D	0.562	neutral	None	None	None	None	N
E/D	0.1373	likely_benign	0.1526	benign	-0.324	Destabilizing	0.425	N	0.335	neutral	N	0.445632561	None	None	N
E/F	0.6654	likely_pathogenic	0.7311	pathogenic	-0.371	Destabilizing	0.944	D	0.624	neutral	None	None	None	None	N
E/G	0.1498	likely_benign	0.1743	benign	-0.424	Destabilizing	0.425	N	0.462	neutral	N	0.485825745	None	None	N
E/H	0.3389	likely_benign	0.3969	ambiguous	-0.339	Destabilizing	0.981	D	0.493	neutral	None	None	None	None	N
E/I	0.3024	likely_benign	0.3603	ambiguous	0.209	Stabilizing	0.543	D	0.529	neutral	None	None	None	None	N
E/K	0.0964	likely_benign	0.1082	benign	0.443	Stabilizing	0.002	N	0.144	neutral	N	0.40116692	None	None	N
E/L	0.3423	ambiguous	0.4077	ambiguous	0.209	Stabilizing	0.329	N	0.448	neutral	None	None	None	None	N
E/M	0.3674	ambiguous	0.4305	ambiguous	0.441	Stabilizing	0.944	D	0.569	neutral	None	None	None	None	N
E/N	0.2033	likely_benign	0.2428	benign	0.29	Stabilizing	0.704	D	0.331	neutral	None	None	None	None	N
E/P	0.5509	ambiguous	0.6209	pathogenic	0.081	Stabilizing	0.828	D	0.485	neutral	None	None	None	None	N
E/Q	0.104	likely_benign	0.1131	benign	0.29	Stabilizing	0.642	D	0.365	neutral	N	0.457196349	None	None	N
E/R	0.1736	likely_benign	0.2004	benign	0.485	Stabilizing	0.543	D	0.347	neutral	None	None	None	None	N
E/S	0.1445	likely_benign	0.1705	benign	0.112	Stabilizing	0.037	N	0.139	neutral	None	None	None	None	N
E/T	0.1414	likely_benign	0.1676	benign	0.256	Stabilizing	0.004	N	0.211	neutral	None	None	None	None	N
E/V	0.1825	likely_benign	0.2133	benign	0.081	Stabilizing	0.01	N	0.283	neutral	N	0.467143983	None	None	N
E/W	0.8588	likely_pathogenic	0.8971	pathogenic	-0.317	Destabilizing	0.995	D	0.567	neutral	None	None	None	None	N
E/Y	0.5397	ambiguous	0.6105	pathogenic	-0.141	Destabilizing	0.981	D	0.597	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.