TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5268	16027;16028;16029	chr2:178733491;178733490;178733489	chr2:179598218;179598217;179598216
N2AB	4951	15076;15077;15078	chr2:178733491;178733490;178733489	chr2:179598218;179598217;179598216
N2A	4024	12295;12296;12297	chr2:178733491;178733490;178733489	chr2:179598218;179598217;179598216
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-36
• Domain position: 8
• Structural Position: 9
• Q(SASA): 0.5399
• 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/Q	None	None	0.961	N	0.472	0.211	0.49530441419	gnomAD-4.0.0	3.42576E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	3.60234E-06	0	1.65959E-05

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	0.1536	likely_benign	0.1563	benign	-0.077	Destabilizing	0.248	N	0.243	neutral	N	0.50471455	None	None	I
E/C	0.8752	likely_pathogenic	0.8752	pathogenic	-0.309	Destabilizing	1.0	D	0.611	neutral	None	None	None	None	I
E/D	0.1127	likely_benign	0.1178	benign	-0.297	Destabilizing	0.98	D	0.491	neutral	N	0.51008613	None	None	I
E/F	0.7893	likely_pathogenic	0.781	pathogenic	-0.04	Destabilizing	0.999	D	0.597	neutral	None	None	None	None	I
E/G	0.1494	likely_benign	0.1436	benign	-0.211	Destabilizing	0.961	D	0.508	neutral	D	0.621783356	None	None	I
E/H	0.4522	ambiguous	0.4477	ambiguous	0.574	Stabilizing	0.999	D	0.449	neutral	None	None	None	None	I
E/I	0.4643	ambiguous	0.4711	ambiguous	0.225	Stabilizing	0.996	D	0.591	neutral	None	None	None	None	I
E/K	0.1453	likely_benign	0.1314	benign	0.319	Stabilizing	0.925	D	0.528	neutral	N	0.49417956	None	None	I
E/L	0.4507	ambiguous	0.4685	ambiguous	0.225	Stabilizing	0.97	D	0.511	neutral	None	None	None	None	I
E/M	0.5342	ambiguous	0.5456	ambiguous	-0.059	Destabilizing	1.0	D	0.568	neutral	None	None	None	None	I
E/N	0.2171	likely_benign	0.2154	benign	0.042	Stabilizing	0.996	D	0.434	neutral	None	None	None	None	I
E/P	0.4203	ambiguous	0.4058	ambiguous	0.143	Stabilizing	0.092	N	0.229	neutral	None	None	None	None	I
E/Q	0.1346	likely_benign	0.1362	benign	0.063	Stabilizing	0.961	D	0.472	neutral	N	0.505913922	None	None	I
E/R	0.2659	likely_benign	0.2415	benign	0.618	Stabilizing	0.191	N	0.215	neutral	None	None	None	None	I
E/S	0.1745	likely_benign	0.1753	benign	-0.106	Destabilizing	0.942	D	0.477	neutral	None	None	None	None	I
E/T	0.2275	likely_benign	0.2319	benign	0.011	Stabilizing	0.97	D	0.509	neutral	None	None	None	None	I
E/V	0.2647	likely_benign	0.2729	benign	0.143	Stabilizing	0.961	D	0.5	neutral	N	0.510515378	None	None	I
E/W	0.9207	likely_pathogenic	0.9151	pathogenic	0.034	Stabilizing	1.0	D	0.681	prob.neutral	None	None	None	None	I
E/Y	0.6799	likely_pathogenic	0.6655	pathogenic	0.186	Stabilizing	0.999	D	0.572	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.