TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25136	75631;75632;75633	chr2:178570726;178570725;178570724	chr2:179435453;179435452;179435451
N2AB	23495	70708;70709;70710	chr2:178570726;178570725;178570724	chr2:179435453;179435452;179435451
N2A	22568	67927;67928;67929	chr2:178570726;178570725;178570724	chr2:179435453;179435452;179435451
N2B	16071	48436;48437;48438	chr2:178570726;178570725;178570724	chr2:179435453;179435452;179435451
Novex-1	16196	48811;48812;48813	chr2:178570726;178570725;178570724	chr2:179435453;179435452;179435451
Novex-2	16263	49012;49013;49014	chr2:178570726;178570725;178570724	chr2:179435453;179435452;179435451
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Ig-134
• Domain position: 26
• Structural Position: 38
• Q(SASA): 0.6098
• 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
Y/N	None	None	0.029	N	0.391	0.141	0.279370189704	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.66327E-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
Y/A	0.2185	likely_benign	0.1947	benign	-0.972	Destabilizing	0.016	N	0.299	neutral	None	None	None	None	N
Y/C	0.0805	likely_benign	0.0786	benign	-0.268	Destabilizing	None	N	0.283	neutral	N	0.516319223	None	None	N
Y/D	0.1773	likely_benign	0.1502	benign	0.711	Stabilizing	0.055	N	0.385	neutral	N	0.451806385	None	None	N
Y/E	0.3336	likely_benign	0.3176	benign	0.731	Stabilizing	0.038	N	0.35	neutral	None	None	None	None	N
Y/F	0.0737	likely_benign	0.0718	benign	-0.271	Destabilizing	0.055	N	0.295	neutral	N	0.478531626	None	None	N
Y/G	0.2344	likely_benign	0.197	benign	-1.192	Destabilizing	0.072	N	0.348	neutral	None	None	None	None	N
Y/H	0.0554	likely_benign	0.0621	benign	0.147	Stabilizing	None	N	0.107	neutral	N	0.441360104	None	None	N
Y/I	0.2427	likely_benign	0.2306	benign	-0.383	Destabilizing	0.038	N	0.32	neutral	None	None	None	None	N
Y/K	0.2552	likely_benign	0.2639	benign	-0.191	Destabilizing	0.072	N	0.353	neutral	None	None	None	None	N
Y/L	0.2212	likely_benign	0.2074	benign	-0.383	Destabilizing	None	N	0.175	neutral	None	None	None	None	N
Y/M	0.4088	ambiguous	0.3785	ambiguous	-0.362	Destabilizing	0.214	N	0.304	neutral	None	None	None	None	N
Y/N	0.0993	likely_benign	0.0917	benign	-0.546	Destabilizing	0.029	N	0.391	neutral	N	0.453230537	None	None	N
Y/P	0.8324	likely_pathogenic	0.8221	pathogenic	-0.563	Destabilizing	0.356	N	0.358	neutral	None	None	None	None	N
Y/Q	0.168	likely_benign	0.1744	benign	-0.428	Destabilizing	0.214	N	0.367	neutral	None	None	None	None	N
Y/R	0.126	likely_benign	0.1417	benign	0.075	Stabilizing	0.214	N	0.371	neutral	None	None	None	None	N
Y/S	0.0932	likely_benign	0.0799	benign	-0.997	Destabilizing	0.002	N	0.261	neutral	N	0.3845226	None	None	N
Y/T	0.1825	likely_benign	0.1649	benign	-0.887	Destabilizing	0.072	N	0.347	neutral	None	None	None	None	N
Y/V	0.2008	likely_benign	0.1936	benign	-0.563	Destabilizing	0.038	N	0.305	neutral	None	None	None	None	N
Y/W	0.2662	likely_benign	0.2659	benign	-0.237	Destabilizing	0.864	D	0.38	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.