TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8837	26734;26735;26736	chr2:178714149;178714148;178714147	chr2:179578876;179578875;179578874
N2AB	8520	25783;25784;25785	chr2:178714149;178714148;178714147	chr2:179578876;179578875;179578874
N2A	7593	23002;23003;23004	chr2:178714149;178714148;178714147	chr2:179578876;179578875;179578874
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-74
• Domain position: 8
• Structural Position: 9
• Q(SASA): 0.7783
• 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	None	None	0.309	N	0.361	0.129	0.477451190609	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
E/D	rs1457622129	None	0.003	D	0.132	0.131	0.252681307341	gnomAD-4.0.0	1.59607E-06	None	None	None	None	N	None	5.70841E-05	0	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	0.0909	likely_benign	0.0881	benign	-0.122	Destabilizing	0.309	N	0.361	neutral	N	0.520071604	None	None	N
E/C	0.6604	likely_pathogenic	0.6442	pathogenic	-0.272	Destabilizing	0.996	D	0.341	neutral	None	None	None	None	N
E/D	0.098	likely_benign	0.1069	benign	-0.367	Destabilizing	0.003	N	0.132	neutral	D	0.525189422	None	None	N
E/F	0.4851	ambiguous	0.4832	ambiguous	-0.108	Destabilizing	0.984	D	0.372	neutral	None	None	None	None	N
E/G	0.0897	likely_benign	0.0857	benign	-0.248	Destabilizing	0.003	N	0.21	neutral	N	0.496608243	None	None	N
E/H	0.2789	likely_benign	0.2721	benign	0.526	Stabilizing	0.984	D	0.392	neutral	None	None	None	None	N
E/I	0.1978	likely_benign	0.2033	benign	0.158	Stabilizing	0.91	D	0.391	neutral	None	None	None	None	N
E/K	0.0848	likely_benign	0.0849	benign	0.34	Stabilizing	0.684	D	0.378	neutral	N	0.491092704	None	None	N
E/L	0.2119	likely_benign	0.2216	benign	0.158	Stabilizing	0.742	D	0.421	neutral	None	None	None	None	N
E/M	0.2918	likely_benign	0.2923	benign	-0.065	Destabilizing	0.996	D	0.348	neutral	None	None	None	None	N
E/N	0.1497	likely_benign	0.1545	benign	0.043	Stabilizing	0.59	D	0.347	neutral	None	None	None	None	N
E/P	0.3268	likely_benign	0.3222	benign	0.083	Stabilizing	0.953	D	0.39	neutral	None	None	None	None	N
E/Q	0.0941	likely_benign	0.0942	benign	0.059	Stabilizing	0.815	D	0.392	neutral	N	0.50331264	None	None	N
E/R	0.1391	likely_benign	0.1318	benign	0.628	Stabilizing	0.953	D	0.389	neutral	None	None	None	None	N
E/S	0.1112	likely_benign	0.1045	benign	-0.09	Destabilizing	0.101	N	0.166	neutral	None	None	None	None	N
E/T	0.1336	likely_benign	0.1326	benign	0.022	Stabilizing	0.037	N	0.174	neutral	None	None	None	None	N
E/V	0.1229	likely_benign	0.1238	benign	0.083	Stabilizing	0.684	D	0.429	neutral	N	0.519244885	None	None	N
E/W	0.7087	likely_pathogenic	0.7077	pathogenic	-0.031	Destabilizing	0.996	D	0.39	neutral	None	None	None	None	N
E/Y	0.3758	ambiguous	0.3734	ambiguous	0.121	Stabilizing	0.984	D	0.373	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.