TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5547	16864;16865;16866	chr2:178732330;178732329;178732328	chr2:179597057;179597056;179597055
N2AB	5230	15913;15914;15915	chr2:178732330;178732329;178732328	chr2:179597057;179597056;179597055
N2A	4303	13132;13133;13134	chr2:178732330;178732329;178732328	chr2:179597057;179597056;179597055
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-39
• Domain position: 5
• Structural Position: 5
• Q(SASA): 0.5304
• 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/K	rs766334270	0.154	0.064	N	0.184	0.226	0.156986980423	gnomAD-2.1.1	4.18E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.57E-05	None	0	0	0
E/K	rs766334270	0.154	0.064	N	0.184	0.226	0.156986980423	gnomAD-4.0.0	6.89766E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.18433E-05	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	0.159	likely_benign	0.16	benign	-0.458	Destabilizing	0.679	D	0.357	neutral	N	0.490070331	None	None	N
E/C	0.7633	likely_pathogenic	0.7803	pathogenic	-0.227	Destabilizing	0.998	D	0.347	neutral	None	None	None	None	N
E/D	0.1366	likely_benign	0.1424	benign	-0.466	Destabilizing	0.514	D	0.326	neutral	N	0.47793054	None	None	N
E/F	0.7087	likely_pathogenic	0.7147	pathogenic	-0.22	Destabilizing	0.96	D	0.381	neutral	None	None	None	None	N
E/G	0.1443	likely_benign	0.1426	benign	-0.678	Destabilizing	0.837	D	0.376	neutral	N	0.504154349	None	None	N
E/H	0.3342	likely_benign	0.3556	ambiguous	0.06	Stabilizing	0.98	D	0.373	neutral	None	None	None	None	N
E/I	0.3724	ambiguous	0.3715	ambiguous	0.094	Stabilizing	0.923	D	0.404	neutral	None	None	None	None	N
E/K	0.1071	likely_benign	0.1076	benign	0.131	Stabilizing	0.064	N	0.184	neutral	N	0.359217858	None	None	N
E/L	0.3538	ambiguous	0.3594	ambiguous	0.094	Stabilizing	0.584	D	0.364	neutral	None	None	None	None	N
E/M	0.428	ambiguous	0.4297	ambiguous	0.137	Stabilizing	0.38	N	0.324	neutral	None	None	None	None	N
E/N	0.2384	likely_benign	0.2481	benign	-0.246	Destabilizing	0.083	N	0.163	neutral	None	None	None	None	N
E/P	0.7822	likely_pathogenic	0.7677	pathogenic	-0.07	Destabilizing	0.993	D	0.429	neutral	None	None	None	None	N
E/Q	0.1027	likely_benign	0.1042	benign	-0.2	Destabilizing	0.837	D	0.299	neutral	N	0.402200631	None	None	N
E/R	0.1711	likely_benign	0.1719	benign	0.443	Stabilizing	0.021	N	0.198	neutral	None	None	None	None	N
E/S	0.1819	likely_benign	0.1847	benign	-0.419	Destabilizing	0.584	D	0.309	neutral	None	None	None	None	N
E/T	0.1942	likely_benign	0.1991	benign	-0.241	Destabilizing	0.083	N	0.181	neutral	None	None	None	None	N
E/V	0.207	likely_benign	0.2046	benign	-0.07	Destabilizing	0.719	D	0.367	neutral	N	0.44933843	None	None	N
E/W	0.7983	likely_pathogenic	0.8064	pathogenic	-0.032	Destabilizing	0.998	D	0.36	neutral	None	None	None	None	N
E/Y	0.5425	ambiguous	0.5541	ambiguous	0.027	Stabilizing	0.993	D	0.381	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.