TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16773	50542;50543;50544	chr2:178612094;178612093;178612092	chr2:179476821;179476820;179476819
N2AB	15132	45619;45620;45621	chr2:178612094;178612093;178612092	chr2:179476821;179476820;179476819
N2A	14205	42838;42839;42840	chr2:178612094;178612093;178612092	chr2:179476821;179476820;179476819
N2B	7708	23347;23348;23349	chr2:178612094;178612093;178612092	chr2:179476821;179476820;179476819
Novex-1	7833	23722;23723;23724	chr2:178612094;178612093;178612092	chr2:179476821;179476820;179476819
Novex-2	7900	23923;23924;23925	chr2:178612094;178612093;178612092	chr2:179476821;179476820;179476819
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Fn3-10
• Domain position: 23
• Structural Position: 25
• Q(SASA): 0.5497
• 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
E/K	rs879025295	None	0.999	N	0.591	0.424	0.328752806141	gnomAD-4.0.0	7.97868E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.43237E-05	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
E/A	0.4227	ambiguous	0.3805	ambiguous	-0.885	Destabilizing	0.999	D	0.734	prob.delet.	N	0.485455584	None	None	N
E/C	0.9606	likely_pathogenic	0.953	pathogenic	-0.658	Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	N
E/D	0.273	likely_benign	0.267	benign	-0.978	Destabilizing	0.999	D	0.468	neutral	N	0.475201763	None	None	N
E/F	0.9189	likely_pathogenic	0.9067	pathogenic	-0.218	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
E/G	0.5139	ambiguous	0.5273	ambiguous	-1.227	Destabilizing	1.0	D	0.759	deleterious	N	0.511386948	None	None	N
E/H	0.8329	likely_pathogenic	0.7882	pathogenic	-0.308	Destabilizing	1.0	D	0.689	prob.neutral	None	None	None	None	N
E/I	0.6267	likely_pathogenic	0.5286	ambiguous	0.05	Stabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
E/K	0.5353	ambiguous	0.4523	ambiguous	-0.875	Destabilizing	0.999	D	0.591	neutral	N	0.451288832	None	None	N
E/L	0.6564	likely_pathogenic	0.5954	pathogenic	0.05	Stabilizing	1.0	D	0.814	deleterious	None	None	None	None	N
E/M	0.69	likely_pathogenic	0.6235	pathogenic	0.33	Stabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
E/N	0.5396	ambiguous	0.5026	ambiguous	-1.27	Destabilizing	1.0	D	0.713	prob.delet.	None	None	None	None	N
E/P	0.9916	likely_pathogenic	0.9906	pathogenic	-0.242	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
E/Q	0.3209	likely_benign	0.2619	benign	-1.134	Destabilizing	1.0	D	0.631	neutral	N	0.475201763	None	None	N
E/R	0.7308	likely_pathogenic	0.6797	pathogenic	-0.421	Destabilizing	1.0	D	0.712	prob.delet.	None	None	None	None	N
E/S	0.5072	ambiguous	0.4644	ambiguous	-1.574	Destabilizing	0.999	D	0.665	neutral	None	None	None	None	N
E/T	0.5468	ambiguous	0.4805	ambiguous	-1.3	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
E/V	0.4386	ambiguous	0.3542	ambiguous	-0.242	Destabilizing	1.0	D	0.799	deleterious	N	0.478394945	None	None	N
E/W	0.9832	likely_pathogenic	0.9812	pathogenic	0.042	Stabilizing	1.0	D	0.832	deleterious	None	None	None	None	N
E/Y	0.8696	likely_pathogenic	0.8602	pathogenic	0.001	Stabilizing	1.0	D	0.805	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.