TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15677	47254;47255;47256	chr2:178618429;178618428;178618427	chr2:179483156;179483155;179483154
N2AB	14036	42331;42332;42333	chr2:178618429;178618428;178618427	chr2:179483156;179483155;179483154
N2A	13109	39550;39551;39552	chr2:178618429;178618428;178618427	chr2:179483156;179483155;179483154
N2B	6612	20059;20060;20061	chr2:178618429;178618428;178618427	chr2:179483156;179483155;179483154
Novex-1	6737	20434;20435;20436	chr2:178618429;178618428;178618427	chr2:179483156;179483155;179483154
Novex-2	6804	20635;20636;20637	chr2:178618429;178618428;178618427	chr2:179483156;179483155;179483154
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCT
• RefSeq wild type template codon: CGA
• Domain: Fn3-1
• Domain position: 21
• Structural Position: 23
• Q(SASA): 0.1794
• 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
A/V	None	None	0.334	N	0.575	0.244	0.37262878642	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	6.07533E-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
A/C	0.3446	ambiguous	0.3622	ambiguous	-0.97	Destabilizing	0.982	D	0.719	prob.delet.	None	None	None	None	N
A/D	0.5107	ambiguous	0.4649	ambiguous	-1.972	Destabilizing	0.638	D	0.724	prob.delet.	N	0.50361351	None	None	N
A/E	0.3253	likely_benign	0.2971	benign	-1.857	Destabilizing	0.826	D	0.661	neutral	None	None	None	None	N
A/F	0.2863	likely_benign	0.2899	benign	-0.755	Destabilizing	0.935	D	0.795	deleterious	None	None	None	None	N
A/G	0.1114	likely_benign	0.1391	benign	-1.334	Destabilizing	0.002	N	0.369	neutral	N	0.512884766	None	None	N
A/H	0.4065	ambiguous	0.3625	ambiguous	-1.816	Destabilizing	0.982	D	0.791	deleterious	None	None	None	None	N
A/I	0.2157	likely_benign	0.2187	benign	0.107	Stabilizing	0.7	D	0.731	prob.delet.	None	None	None	None	N
A/K	0.3495	ambiguous	0.3286	benign	-1.212	Destabilizing	0.7	D	0.671	neutral	None	None	None	None	N
A/L	0.1672	likely_benign	0.1624	benign	0.107	Stabilizing	0.399	N	0.605	neutral	None	None	None	None	N
A/M	0.2099	likely_benign	0.2267	benign	-0.024	Destabilizing	0.982	D	0.749	deleterious	None	None	None	None	N
A/N	0.2881	likely_benign	0.2755	benign	-1.263	Destabilizing	0.7	D	0.752	deleterious	None	None	None	None	N
A/P	0.9735	likely_pathogenic	0.9439	pathogenic	-0.193	Destabilizing	0.781	D	0.727	prob.delet.	D	0.620498007	None	None	N
A/Q	0.2671	likely_benign	0.2495	benign	-1.202	Destabilizing	0.826	D	0.763	deleterious	None	None	None	None	N
A/R	0.306	likely_benign	0.2579	benign	-1.157	Destabilizing	0.826	D	0.728	prob.delet.	None	None	None	None	N
A/S	0.0914	likely_benign	0.0935	benign	-1.637	Destabilizing	0.201	N	0.5	neutral	N	0.408362896	None	None	N
A/T	0.0941	likely_benign	0.0875	benign	-1.411	Destabilizing	0.015	N	0.414	neutral	N	0.444868242	None	None	N
A/V	0.1379	likely_benign	0.1366	benign	-0.193	Destabilizing	0.334	N	0.575	neutral	N	0.481761183	None	None	N
A/W	0.7179	likely_pathogenic	0.6739	pathogenic	-1.455	Destabilizing	0.982	D	0.764	deleterious	None	None	None	None	N
A/Y	0.4136	ambiguous	0.4147	ambiguous	-0.899	Destabilizing	0.935	D	0.801	deleterious	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.