TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18151	54676;54677;54678	chr2:178604236;178604235;178604234	chr2:179468963;179468962;179468961
N2AB	16510	49753;49754;49755	chr2:178604236;178604235;178604234	chr2:179468963;179468962;179468961
N2A	15583	46972;46973;46974	chr2:178604236;178604235;178604234	chr2:179468963;179468962;179468961
N2B	9086	27481;27482;27483	chr2:178604236;178604235;178604234	chr2:179468963;179468962;179468961
Novex-1	9211	27856;27857;27858	chr2:178604236;178604235;178604234	chr2:179468963;179468962;179468961
Novex-2	9278	28057;28058;28059	chr2:178604236;178604235;178604234	chr2:179468963;179468962;179468961
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: Fn3-19
• Domain position: 87
• Structural Position: 119
• Q(SASA): 0.3961
• 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/G	None	None	0.996	N	0.723	0.357	0.352910780287	gnomAD-4.0.0	6.93126E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.08031E-07	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	0.2251	likely_benign	0.1966	benign	-0.433	Destabilizing	0.998	D	0.709	prob.delet.	N	0.487883749	None	None	N
D/C	0.7876	likely_pathogenic	0.74	pathogenic	-0.094	Destabilizing	1.0	D	0.79	deleterious	None	None	None	None	N
D/E	0.149	likely_benign	0.133	benign	-0.536	Destabilizing	0.619	D	0.293	neutral	N	0.401072841	None	None	N
D/F	0.8027	likely_pathogenic	0.7485	pathogenic	-0.325	Destabilizing	1.0	D	0.808	deleterious	None	None	None	None	N
D/G	0.2552	likely_benign	0.2268	benign	-0.678	Destabilizing	0.996	D	0.723	prob.delet.	N	0.460703134	None	None	N
D/H	0.5047	ambiguous	0.4506	ambiguous	-0.43	Destabilizing	1.0	D	0.771	deleterious	N	0.461463602	None	None	N
D/I	0.6044	likely_pathogenic	0.5111	ambiguous	0.179	Stabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
D/K	0.4823	ambiguous	0.4287	ambiguous	-0.054	Destabilizing	0.998	D	0.734	prob.delet.	None	None	None	None	N
D/L	0.5181	ambiguous	0.4587	ambiguous	0.179	Stabilizing	0.999	D	0.805	deleterious	None	None	None	None	N
D/M	0.7397	likely_pathogenic	0.6804	pathogenic	0.438	Stabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
D/N	0.1417	likely_benign	0.122	benign	-0.318	Destabilizing	0.999	D	0.733	prob.delet.	N	0.513704913	None	None	N
D/P	0.5706	likely_pathogenic	0.5447	ambiguous	-0.001	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
D/Q	0.459	ambiguous	0.4079	ambiguous	-0.28	Destabilizing	0.998	D	0.773	deleterious	None	None	None	None	N
D/R	0.5716	likely_pathogenic	0.5228	ambiguous	0.102	Stabilizing	0.998	D	0.781	deleterious	None	None	None	None	N
D/S	0.1644	likely_benign	0.145	benign	-0.472	Destabilizing	0.994	D	0.711	prob.delet.	None	None	None	None	N
D/T	0.3484	ambiguous	0.2854	benign	-0.287	Destabilizing	0.999	D	0.783	deleterious	None	None	None	None	N
D/V	0.3732	ambiguous	0.3089	benign	-0.001	Destabilizing	0.999	D	0.813	deleterious	N	0.506989585	None	None	N
D/W	0.9337	likely_pathogenic	0.9226	pathogenic	-0.184	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
D/Y	0.4504	ambiguous	0.404	ambiguous	-0.098	Destabilizing	1.0	D	0.807	deleterious	N	0.467958062	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.