TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2237	6934;6935;6936	chr2:178775002;178775001;178775000	chr2:179639729;179639728;179639727
N2AB	2237	6934;6935;6936	chr2:178775002;178775001;178775000	chr2:179639729;179639728;179639727
N2A	2237	6934;6935;6936	chr2:178775002;178775001;178775000	chr2:179639729;179639728;179639727
N2B	2191	6796;6797;6798	chr2:178775002;178775001;178775000	chr2:179639729;179639728;179639727
Novex-1	2191	6796;6797;6798	chr2:178775002;178775001;178775000	chr2:179639729;179639728;179639727
Novex-2	2191	6796;6797;6798	chr2:178775002;178775001;178775000	chr2:179639729;179639728;179639727
Novex-3	2237	6934;6935;6936	chr2:178775002;178775001;178775000	chr2:179639729;179639728;179639727

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Ig-11
• Domain position: 64
• Structural Position: 145
• Q(SASA): 0.3717
• 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
D/V	None	None	0.984	N	0.585	0.443	0.631027719221	gnomAD-4.0.0	1.59083E-06	None	None	None	None	N	None	0	0	None	0	2.77531E-05	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
D/A	0.1498	likely_benign	0.153	benign	-0.373	Destabilizing	0.896	D	0.492	neutral	N	0.491522583	None	None	N
D/C	0.5468	ambiguous	0.5449	ambiguous	0.177	Stabilizing	0.999	D	0.729	prob.delet.	None	None	None	None	N
D/E	0.1353	likely_benign	0.1384	benign	-0.427	Destabilizing	0.011	N	0.108	neutral	N	0.437262509	None	None	N
D/F	0.5154	ambiguous	0.5149	ambiguous	-0.413	Destabilizing	0.996	D	0.655	neutral	None	None	None	None	N
D/G	0.1321	likely_benign	0.1361	benign	-0.605	Destabilizing	0.896	D	0.421	neutral	N	0.494912087	None	None	N
D/H	0.2072	likely_benign	0.2102	benign	-0.562	Destabilizing	0.984	D	0.519	neutral	N	0.512649789	None	None	N
D/I	0.3507	ambiguous	0.3512	ambiguous	0.202	Stabilizing	0.988	D	0.653	neutral	None	None	None	None	N
D/K	0.2491	likely_benign	0.2615	benign	0.253	Stabilizing	0.851	D	0.421	neutral	None	None	None	None	N
D/L	0.3181	likely_benign	0.3232	benign	0.202	Stabilizing	0.976	D	0.587	neutral	None	None	None	None	N
D/M	0.515	ambiguous	0.5182	ambiguous	0.594	Stabilizing	0.999	D	0.653	neutral	None	None	None	None	N
D/N	0.0749	likely_benign	0.075	benign	-0.08	Destabilizing	0.103	N	0.241	neutral	N	0.493720086	None	None	N
D/P	0.8887	likely_pathogenic	0.8888	pathogenic	0.034	Stabilizing	0.988	D	0.501	neutral	None	None	None	None	N
D/Q	0.237	likely_benign	0.2436	benign	-0.027	Destabilizing	0.851	D	0.419	neutral	None	None	None	None	N
D/R	0.2987	likely_benign	0.3083	benign	0.261	Stabilizing	0.976	D	0.545	neutral	None	None	None	None	N
D/S	0.0965	likely_benign	0.0962	benign	-0.195	Destabilizing	0.919	D	0.367	neutral	None	None	None	None	N
D/T	0.1791	likely_benign	0.1775	benign	-0.008	Destabilizing	0.919	D	0.461	neutral	None	None	None	None	N
D/V	0.2288	likely_benign	0.2313	benign	0.034	Stabilizing	0.984	D	0.585	neutral	N	0.455821238	None	None	N
D/W	0.8677	likely_pathogenic	0.8697	pathogenic	-0.311	Destabilizing	0.999	D	0.733	prob.delet.	None	None	None	None	N
D/Y	0.235	likely_benign	0.2423	benign	-0.184	Destabilizing	0.995	D	0.657	neutral	N	0.511365707	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.