TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2268	7027;7028;7029	chr2:178774462;178774461;178774460	chr2:179639189;179639188;179639187
N2AB	2268	7027;7028;7029	chr2:178774462;178774461;178774460	chr2:179639189;179639188;179639187
N2A	2268	7027;7028;7029	chr2:178774462;178774461;178774460	chr2:179639189;179639188;179639187
N2B	2222	6889;6890;6891	chr2:178774462;178774461;178774460	chr2:179639189;179639188;179639187
Novex-1	2222	6889;6890;6891	chr2:178774462;178774461;178774460	chr2:179639189;179639188;179639187
Novex-2	2222	6889;6890;6891	chr2:178774462;178774461;178774460	chr2:179639189;179639188;179639187
Novex-3	2268	7027;7028;7029	chr2:178774462;178774461;178774460	chr2:179639189;179639188;179639187

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Ig-12
• Domain position: 2
• Structural Position: 2
• Q(SASA): 0.657
• 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/G	rs1288686465	-0.585	0.999	D	0.627	0.618	0.580444438771	gnomAD-2.1.1	3.18E-05	None	None	None	None	N	None	1.14732E-04	0	None	0	0	None	0	None	0	0	0
E/Q	None	None	0.999	N	0.646	0.303	0.29385284311	gnomAD-4.0.0	1.59429E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	2.41313E-04	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	0.1821	likely_benign	0.1665	benign	-0.316	Destabilizing	0.998	D	0.609	neutral	N	0.511726249	None	None	N
E/C	0.8491	likely_pathogenic	0.817	pathogenic	-0.174	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
E/D	0.1233	likely_benign	0.109	benign	-0.315	Destabilizing	0.434	N	0.185	neutral	N	0.512020307	None	None	N
E/F	0.7684	likely_pathogenic	0.7432	pathogenic	-0.035	Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	N
E/G	0.2066	likely_benign	0.1938	benign	-0.527	Destabilizing	0.999	D	0.627	neutral	D	0.582640651	None	None	N
E/H	0.4292	ambiguous	0.3906	ambiguous	0.299	Stabilizing	1.0	D	0.701	prob.neutral	None	None	None	None	N
E/I	0.4183	ambiguous	0.3849	ambiguous	0.209	Stabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	N
E/K	0.1819	likely_benign	0.1716	benign	0.356	Stabilizing	0.998	D	0.533	neutral	N	0.481867867	None	None	N
E/L	0.5023	ambiguous	0.4661	ambiguous	0.209	Stabilizing	1.0	D	0.711	prob.delet.	None	None	None	None	N
E/M	0.531	ambiguous	0.4877	ambiguous	0.167	Stabilizing	1.0	D	0.712	prob.delet.	None	None	None	None	N
E/N	0.1985	likely_benign	0.1819	benign	-0.12	Destabilizing	0.999	D	0.71	prob.delet.	None	None	None	None	N
E/P	0.8597	likely_pathogenic	0.8538	pathogenic	0.054	Stabilizing	1.0	D	0.677	prob.neutral	None	None	None	None	N
E/Q	0.155	likely_benign	0.1369	benign	-0.047	Destabilizing	0.999	D	0.646	neutral	N	0.508220491	None	None	N
E/R	0.3134	likely_benign	0.2904	benign	0.629	Stabilizing	1.0	D	0.694	prob.neutral	None	None	None	None	N
E/S	0.1649	likely_benign	0.1506	benign	-0.258	Destabilizing	0.997	D	0.571	neutral	None	None	None	None	N
E/T	0.1793	likely_benign	0.161	benign	-0.074	Destabilizing	1.0	D	0.689	prob.neutral	None	None	None	None	N
E/V	0.2497	likely_benign	0.2275	benign	0.054	Stabilizing	1.0	D	0.671	neutral	D	0.534342394	None	None	N
E/W	0.9203	likely_pathogenic	0.9006	pathogenic	0.153	Stabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
E/Y	0.6205	likely_pathogenic	0.5875	pathogenic	0.219	Stabilizing	1.0	D	0.717	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.