TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20600	62023;62024;62025	chr2:178589927;178589926;178589925	chr2:179454654;179454653;179454652
N2AB	18959	57100;57101;57102	chr2:178589927;178589926;178589925	chr2:179454654;179454653;179454652
N2A	18032	54319;54320;54321	chr2:178589927;178589926;178589925	chr2:179454654;179454653;179454652
N2B	11535	34828;34829;34830	chr2:178589927;178589926;178589925	chr2:179454654;179454653;179454652
Novex-1	11660	35203;35204;35205	chr2:178589927;178589926;178589925	chr2:179454654;179454653;179454652
Novex-2	11727	35404;35405;35406	chr2:178589927;178589926;178589925	chr2:179454654;179454653;179454652
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: Fn3-37
• Domain position: 32
• Structural Position: 34
• Q(SASA): 0.9491
• 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	rs1337048658	0.202	0.999	N	0.469	0.144	0.311691414656	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	2.91E-05	None	0	0	None	0	None	0	0	0
E/D	rs1337048658	0.202	0.999	N	0.469	0.144	0.311691414656	gnomAD-4.0.0	1.59248E-06	None	None	None	None	I	None	0	2.28885E-05	None	0	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	0.4063	ambiguous	0.4468	ambiguous	-0.292	Destabilizing	0.999	D	0.611	neutral	N	0.507149874	None	None	I
E/C	0.967	likely_pathogenic	0.9732	pathogenic	None	Stabilizing	1.0	D	0.687	prob.neutral	None	None	None	None	I
E/D	0.1582	likely_benign	0.1572	benign	-0.208	Destabilizing	0.999	D	0.469	neutral	N	0.477000326	None	None	I
E/F	0.9557	likely_pathogenic	0.9657	pathogenic	-0.224	Destabilizing	1.0	D	0.604	neutral	None	None	None	None	I
E/G	0.5287	ambiguous	0.5682	pathogenic	-0.472	Destabilizing	1.0	D	0.617	neutral	N	0.482399603	None	None	I
E/H	0.8543	likely_pathogenic	0.8815	pathogenic	0.058	Stabilizing	1.0	D	0.663	neutral	None	None	None	None	I
E/I	0.7642	likely_pathogenic	0.7923	pathogenic	0.139	Stabilizing	1.0	D	0.629	neutral	None	None	None	None	I
E/K	0.5464	ambiguous	0.5779	pathogenic	0.357	Stabilizing	0.999	D	0.616	neutral	N	0.498549034	None	None	I
E/L	0.7906	likely_pathogenic	0.8226	pathogenic	0.139	Stabilizing	1.0	D	0.645	neutral	None	None	None	None	I
E/M	0.8265	likely_pathogenic	0.8554	pathogenic	0.197	Stabilizing	1.0	D	0.623	neutral	None	None	None	None	I
E/N	0.5466	ambiguous	0.5853	pathogenic	0.124	Stabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	I
E/P	0.6229	likely_pathogenic	0.6381	pathogenic	0.015	Stabilizing	1.0	D	0.656	neutral	None	None	None	None	I
E/Q	0.3961	ambiguous	0.4582	ambiguous	0.153	Stabilizing	1.0	D	0.62	neutral	D	0.524831558	None	None	I
E/R	0.6938	likely_pathogenic	0.7299	pathogenic	0.552	Stabilizing	1.0	D	0.718	prob.delet.	None	None	None	None	I
E/S	0.5048	ambiguous	0.5441	ambiguous	-0.06	Destabilizing	0.999	D	0.65	neutral	None	None	None	None	I
E/T	0.5745	likely_pathogenic	0.6168	pathogenic	0.087	Stabilizing	1.0	D	0.669	neutral	None	None	None	None	I
E/V	0.5468	ambiguous	0.5899	pathogenic	0.015	Stabilizing	1.0	D	0.677	prob.neutral	N	0.485424569	None	None	I
E/W	0.9885	likely_pathogenic	0.9909	pathogenic	-0.102	Destabilizing	1.0	D	0.69	prob.neutral	None	None	None	None	I
E/Y	0.9201	likely_pathogenic	0.9361	pathogenic	0.014	Stabilizing	1.0	D	0.639	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.