TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15244	45955;45956;45957	chr2:178620880;178620879;178620878	chr2:179485607;179485606;179485605
N2AB	13603	41032;41033;41034	chr2:178620880;178620879;178620878	chr2:179485607;179485606;179485605
N2A	12676	38251;38252;38253	chr2:178620880;178620879;178620878	chr2:179485607;179485606;179485605
N2B	6179	18760;18761;18762	chr2:178620880;178620879;178620878	chr2:179485607;179485606;179485605
Novex-1	6304	19135;19136;19137	chr2:178620880;178620879;178620878	chr2:179485607;179485606;179485605
Novex-2	6371	19336;19337;19338	chr2:178620880;178620879;178620878	chr2:179485607;179485606;179485605
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-104
• Domain position: 37
• Structural Position: 52
• Q(SASA): 0.7713
• 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/A	rs759829017	0.092	0.027	N	0.335	0.108	0.165133752707	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.95E-06	0
E/A	rs759829017	0.092	0.027	N	0.335	0.108	0.165133752707	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
E/A	rs759829017	0.092	0.027	N	0.335	0.108	0.165133752707	gnomAD-4.0.0	5.13219E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.58672E-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	0.1804	likely_benign	0.1973	benign	-0.66	Destabilizing	0.027	N	0.335	neutral	N	0.453933624	None	None	N
E/C	0.8645	likely_pathogenic	0.8789	pathogenic	-0.279	Destabilizing	0.935	D	0.408	neutral	None	None	None	None	N
E/D	0.0751	likely_benign	0.0856	benign	-0.465	Destabilizing	None	N	0.139	neutral	N	0.402141526	None	None	N
E/F	0.8187	likely_pathogenic	0.8284	pathogenic	-0.399	Destabilizing	0.791	D	0.406	neutral	None	None	None	None	N
E/G	0.0888	likely_benign	0.0928	benign	-0.887	Destabilizing	None	N	0.179	neutral	N	0.332530399	None	None	N
E/H	0.4483	ambiguous	0.4809	ambiguous	-0.195	Destabilizing	0.555	D	0.341	neutral	None	None	None	None	N
E/I	0.546	ambiguous	0.5838	pathogenic	-0.081	Destabilizing	0.555	D	0.433	neutral	None	None	None	None	N
E/K	0.1168	likely_benign	0.1206	benign	-0.057	Destabilizing	None	N	0.153	neutral	N	0.446215387	None	None	N
E/L	0.5356	ambiguous	0.5582	ambiguous	-0.081	Destabilizing	0.149	N	0.477	neutral	None	None	None	None	N
E/M	0.5419	ambiguous	0.5706	pathogenic	0.087	Stabilizing	0.935	D	0.39	neutral	None	None	None	None	N
E/N	0.1381	likely_benign	0.16	benign	-0.382	Destabilizing	0.002	N	0.161	neutral	None	None	None	None	N
E/P	0.7196	likely_pathogenic	0.7392	pathogenic	-0.254	Destabilizing	0.555	D	0.423	neutral	None	None	None	None	N
E/Q	0.1454	likely_benign	0.1511	benign	-0.331	Destabilizing	0.117	N	0.377	neutral	N	0.449100201	None	None	N
E/R	0.215	likely_benign	0.2176	benign	0.257	Stabilizing	0.081	N	0.361	neutral	None	None	None	None	N
E/S	0.1532	likely_benign	0.1698	benign	-0.587	Destabilizing	0.035	N	0.286	neutral	None	None	None	None	N
E/T	0.2454	likely_benign	0.2712	benign	-0.402	Destabilizing	0.149	N	0.405	neutral	None	None	None	None	N
E/V	0.3696	ambiguous	0.3961	ambiguous	-0.254	Destabilizing	0.117	N	0.451	neutral	N	0.451541198	None	None	N
E/W	0.8874	likely_pathogenic	0.8911	pathogenic	-0.181	Destabilizing	0.935	D	0.459	neutral	None	None	None	None	N
E/Y	0.6608	likely_pathogenic	0.6828	pathogenic	-0.157	Destabilizing	0.791	D	0.395	neutral	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.