TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6268	19027;19028;19029	chr2:178729354;178729353;178729352	chr2:179594081;179594080;179594079
N2AB	5951	18076;18077;18078	chr2:178729354;178729353;178729352	chr2:179594081;179594080;179594079
N2A	5024	15295;15296;15297	chr2:178729354;178729353;178729352	chr2:179594081;179594080;179594079
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: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-46
• Domain position: 70
• Structural Position: 153
• Q(SASA): 0.4759
• 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/V	rs1378963436	-0.334	0.015	N	0.423	0.355	0.505765104075	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	9.98E-05	0	None	0	None	0	0	0
E/V	rs1378963436	-0.334	0.015	N	0.423	0.355	0.505765104075	gnomAD-4.0.0	1.59178E-06	None	None	None	None	N	None	0	0	None	4.77145E-05	0	None	0	0	0	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	0.1951	likely_benign	0.1663	benign	-0.816	Destabilizing	0.334	N	0.622	neutral	N	0.507854455	None	None	N
E/C	0.8507	likely_pathogenic	0.8167	pathogenic	-0.295	Destabilizing	0.982	D	0.715	prob.delet.	None	None	None	None	N
E/D	0.0831	likely_benign	0.0841	benign	-1.016	Destabilizing	0.002	N	0.389	neutral	N	0.487729899	None	None	N
E/F	0.6097	likely_pathogenic	0.5665	pathogenic	-0.6	Destabilizing	0.826	D	0.735	prob.delet.	None	None	None	None	N
E/G	0.2401	likely_benign	0.2007	benign	-1.139	Destabilizing	0.334	N	0.649	neutral	N	0.511522947	None	None	N
E/H	0.4652	ambiguous	0.3989	ambiguous	-0.961	Destabilizing	0.947	D	0.646	neutral	None	None	None	None	N
E/I	0.2407	likely_benign	0.2182	benign	0.048	Stabilizing	0.539	D	0.705	prob.neutral	None	None	None	None	N
E/K	0.2043	likely_benign	0.1645	benign	-0.397	Destabilizing	0.334	N	0.602	neutral	N	0.494269083	None	None	N
E/L	0.3262	likely_benign	0.2937	benign	0.048	Stabilizing	0.25	N	0.654	neutral	None	None	None	None	N
E/M	0.3924	ambiguous	0.3552	ambiguous	0.561	Stabilizing	0.947	D	0.723	prob.delet.	None	None	None	None	N
E/N	0.1876	likely_benign	0.1669	benign	-0.768	Destabilizing	0.539	D	0.646	neutral	None	None	None	None	N
E/P	0.642	likely_pathogenic	0.5548	ambiguous	-0.219	Destabilizing	0.826	D	0.747	deleterious	None	None	None	None	N
E/Q	0.1779	likely_benign	0.1506	benign	-0.674	Destabilizing	0.638	D	0.637	neutral	N	0.521418398	None	None	N
E/R	0.3415	ambiguous	0.2814	benign	-0.3	Destabilizing	0.7	D	0.662	neutral	None	None	None	None	N
E/S	0.2119	likely_benign	0.1833	benign	-1.052	Destabilizing	0.25	N	0.599	neutral	None	None	None	None	N
E/T	0.2145	likely_benign	0.1896	benign	-0.781	Destabilizing	0.399	N	0.673	neutral	None	None	None	None	N
E/V	0.1672	likely_benign	0.1509	benign	-0.219	Destabilizing	0.015	N	0.423	neutral	N	0.495541306	None	None	N
E/W	0.828	likely_pathogenic	0.7949	pathogenic	-0.427	Destabilizing	0.982	D	0.681	prob.neutral	None	None	None	None	N
E/Y	0.4918	ambiguous	0.4483	ambiguous	-0.356	Destabilizing	0.935	D	0.739	prob.delet.	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.