TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20053	60382;60383;60384	chr2:178591662;178591661;178591660	chr2:179456389;179456388;179456387
N2AB	18412	55459;55460;55461	chr2:178591662;178591661;178591660	chr2:179456389;179456388;179456387
N2A	17485	52678;52679;52680	chr2:178591662;178591661;178591660	chr2:179456389;179456388;179456387
N2B	10988	33187;33188;33189	chr2:178591662;178591661;178591660	chr2:179456389;179456388;179456387
Novex-1	11113	33562;33563;33564	chr2:178591662;178591661;178591660	chr2:179456389;179456388;179456387
Novex-2	11180	33763;33764;33765	chr2:178591662;178591661;178591660	chr2:179456389;179456388;179456387
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: Fn3-33
• Domain position: 77
• Structural Position: 111
• Q(SASA): 0.3408
• 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/G	None	None	0.505	N	0.657	0.341	0.470810165807	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	0.2546	likely_benign	0.2769	benign	-0.87	Destabilizing	0.338	N	0.553	neutral	N	0.464511031	None	None	I
E/C	0.8583	likely_pathogenic	0.8774	pathogenic	-0.441	Destabilizing	0.991	D	0.768	deleterious	None	None	None	None	I
E/D	0.6498	likely_pathogenic	0.723	pathogenic	-1.28	Destabilizing	0.296	N	0.441	neutral	N	0.477787566	None	None	I
E/F	0.8837	likely_pathogenic	0.8998	pathogenic	-0.882	Destabilizing	0.967	D	0.795	deleterious	None	None	None	None	I
E/G	0.399	ambiguous	0.4503	ambiguous	-1.202	Destabilizing	0.505	D	0.657	neutral	N	0.472191705	None	None	I
E/H	0.626	likely_pathogenic	0.6826	pathogenic	-1.163	Destabilizing	0.826	D	0.574	neutral	None	None	None	None	I
E/I	0.4352	ambiguous	0.4688	ambiguous	0.029	Stabilizing	0.906	D	0.805	deleterious	None	None	None	None	I
E/K	0.1541	likely_benign	0.1727	benign	-0.543	Destabilizing	0.174	N	0.479	neutral	N	0.492140349	None	None	I
E/L	0.5189	ambiguous	0.5692	pathogenic	0.029	Stabilizing	0.575	D	0.697	prob.neutral	None	None	None	None	I
E/M	0.474	ambiguous	0.5039	ambiguous	0.573	Stabilizing	0.973	D	0.77	deleterious	None	None	None	None	I
E/N	0.6147	likely_pathogenic	0.6818	pathogenic	-0.885	Destabilizing	0.575	D	0.535	neutral	None	None	None	None	I
E/P	0.9872	likely_pathogenic	0.9912	pathogenic	-0.25	Destabilizing	0.906	D	0.713	prob.delet.	None	None	None	None	I
E/Q	0.0895	likely_benign	0.0953	benign	-0.789	Destabilizing	0.001	N	0.151	neutral	N	0.481115279	None	None	I
E/R	0.2595	likely_benign	0.3005	benign	-0.495	Destabilizing	0.404	N	0.519	neutral	None	None	None	None	I
E/S	0.3833	ambiguous	0.4267	ambiguous	-1.264	Destabilizing	0.404	N	0.461	neutral	None	None	None	None	I
E/T	0.3308	likely_benign	0.3773	ambiguous	-0.972	Destabilizing	0.575	D	0.643	neutral	None	None	None	None	I
E/V	0.2745	likely_benign	0.2913	benign	-0.25	Destabilizing	0.782	D	0.703	prob.neutral	N	0.407900026	None	None	I
E/W	0.9496	likely_pathogenic	0.9598	pathogenic	-0.823	Destabilizing	0.991	D	0.767	deleterious	None	None	None	None	I
E/Y	0.7974	likely_pathogenic	0.8357	pathogenic	-0.64	Destabilizing	0.906	D	0.789	deleterious	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.