TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23381	70366;70367;70368	chr2:178575991;178575990;178575989	chr2:179440718;179440717;179440716
N2AB	21740	65443;65444;65445	chr2:178575991;178575990;178575989	chr2:179440718;179440717;179440716
N2A	20813	62662;62663;62664	chr2:178575991;178575990;178575989	chr2:179440718;179440717;179440716
N2B	14316	43171;43172;43173	chr2:178575991;178575990;178575989	chr2:179440718;179440717;179440716
Novex-1	14441	43546;43547;43548	chr2:178575991;178575990;178575989	chr2:179440718;179440717;179440716
Novex-2	14508	43747;43748;43749	chr2:178575991;178575990;178575989	chr2:179440718;179440717;179440716
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Ig-129
• Domain position: 37
• Structural Position: 51
• Q(SASA): 0.5843
• Predicted PPI site: I

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
D/N	rs1559456668	None	0.801	N	0.389	0.269	0.236278675362	gnomAD-4.0.0	3.19209E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	5.7405E-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
D/A	0.264	likely_benign	0.3198	benign	-0.196	Destabilizing	0.051	N	0.264	neutral	N	0.501466335	None	None	I
D/C	0.7592	likely_pathogenic	0.8011	pathogenic	0.096	Stabilizing	0.998	D	0.485	neutral	None	None	None	None	I
D/E	0.1439	likely_benign	0.1521	benign	-0.221	Destabilizing	0.051	N	0.209	neutral	N	0.45015208	None	None	I
D/F	0.7994	likely_pathogenic	0.8534	pathogenic	-0.206	Destabilizing	0.991	D	0.483	neutral	None	None	None	None	I
D/G	0.1698	likely_benign	0.1956	benign	-0.364	Destabilizing	0.005	N	0.183	neutral	N	0.47300751	None	None	I
D/H	0.5301	ambiguous	0.5959	pathogenic	0.006	Stabilizing	0.997	D	0.367	neutral	N	0.491832307	None	None	I
D/I	0.6424	likely_pathogenic	0.7176	pathogenic	0.191	Stabilizing	0.974	D	0.493	neutral	None	None	None	None	I
D/K	0.5583	ambiguous	0.6194	pathogenic	0.457	Stabilizing	0.842	D	0.4	neutral	None	None	None	None	I
D/L	0.5925	likely_pathogenic	0.6554	pathogenic	0.191	Stabilizing	0.949	D	0.479	neutral	None	None	None	None	I
D/M	0.7452	likely_pathogenic	0.7859	pathogenic	0.276	Stabilizing	0.998	D	0.475	neutral	None	None	None	None	I
D/N	0.1533	likely_benign	0.1647	benign	0.169	Stabilizing	0.801	D	0.389	neutral	N	0.472388648	None	None	I
D/P	0.7566	likely_pathogenic	0.8299	pathogenic	0.083	Stabilizing	0.974	D	0.372	neutral	None	None	None	None	I
D/Q	0.4478	ambiguous	0.4943	ambiguous	0.197	Stabilizing	0.949	D	0.333	neutral	None	None	None	None	I
D/R	0.6098	likely_pathogenic	0.6775	pathogenic	0.565	Stabilizing	0.949	D	0.467	neutral	None	None	None	None	I
D/S	0.2257	likely_benign	0.2651	benign	0.085	Stabilizing	0.525	D	0.317	neutral	None	None	None	None	I
D/T	0.4302	ambiguous	0.5073	ambiguous	0.219	Stabilizing	0.842	D	0.409	neutral	None	None	None	None	I
D/V	0.4105	ambiguous	0.4941	ambiguous	0.083	Stabilizing	0.801	D	0.486	neutral	N	0.507912305	None	None	I
D/W	0.9341	likely_pathogenic	0.9533	pathogenic	-0.105	Destabilizing	0.998	D	0.54	neutral	None	None	None	None	I
D/Y	0.4393	ambiguous	0.5188	ambiguous	0.026	Stabilizing	0.989	D	0.475	neutral	N	0.492085797	None	None	I

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.