TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7784	23575;23576;23577	chr2:178720412;178720411;178720410	chr2:179585139;179585138;179585137
N2AB	7467	22624;22625;22626	chr2:178720412;178720411;178720410	chr2:179585139;179585138;179585137
N2A	6540	19843;19844;19845	chr2:178720412;178720411;178720410	chr2:179585139;179585138;179585137
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACG
• RefSeq wild type template codon: TGC
• Domain: Ig-62
• Domain position: 83
• Structural Position: 168
• Q(SASA): 0.2968
• 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
T/K	None	None	0.224	N	0.466	0.179	0.459370960843	gnomAD-4.0.0	1.36909E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.7995E-06	0	0
T/M	rs745569991	0.089	0.901	N	0.539	0.263	0.746022067851	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.28E-05	None	0	0	0
T/M	rs745569991	0.089	0.901	N	0.539	0.263	0.746022067851	gnomAD-4.0.0	1.36909E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99751E-07	1.16104E-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
T/A	0.0987	likely_benign	0.0792	benign	-0.829	Destabilizing	0.003	N	0.435	neutral	N	0.48621667	None	None	N
T/C	0.4899	ambiguous	0.3826	ambiguous	-0.427	Destabilizing	0.857	D	0.529	neutral	None	None	None	None	N
T/D	0.4432	ambiguous	0.3662	ambiguous	-0.189	Destabilizing	0.031	N	0.462	neutral	None	None	None	None	N
T/E	0.4205	ambiguous	0.3682	ambiguous	-0.2	Destabilizing	0.097	N	0.462	neutral	None	None	None	None	N
T/F	0.1673	likely_benign	0.1328	benign	-0.922	Destabilizing	0.738	D	0.588	neutral	None	None	None	None	N
T/G	0.2863	likely_benign	0.2179	benign	-1.077	Destabilizing	0.213	N	0.523	neutral	None	None	None	None	N
T/H	0.2811	likely_benign	0.2346	benign	-1.313	Destabilizing	0.681	D	0.576	neutral	None	None	None	None	N
T/I	0.1167	likely_benign	0.0957	benign	-0.261	Destabilizing	0.131	N	0.484	neutral	None	None	None	None	N
T/K	0.3388	likely_benign	0.3051	benign	-0.776	Destabilizing	0.224	N	0.466	neutral	N	0.516532654	None	None	N
T/L	0.1027	likely_benign	0.0874	benign	-0.261	Destabilizing	0.058	N	0.493	neutral	None	None	None	None	N
T/M	0.0997	likely_benign	0.0856	benign	0.042	Stabilizing	0.901	D	0.539	neutral	N	0.491523042	None	None	N
T/N	0.1285	likely_benign	0.1062	benign	-0.655	Destabilizing	None	N	0.297	neutral	None	None	None	None	N
T/P	0.4287	ambiguous	0.3523	ambiguous	-0.418	Destabilizing	0.257	N	0.551	neutral	N	0.507652288	None	None	N
T/Q	0.3266	likely_benign	0.2798	benign	-0.82	Destabilizing	0.33	N	0.557	neutral	None	None	None	None	N
T/R	0.2614	likely_benign	0.2367	benign	-0.498	Destabilizing	0.844	D	0.549	neutral	N	0.487751329	None	None	N
T/S	0.0995	likely_benign	0.0818	benign	-0.928	Destabilizing	None	N	0.182	neutral	N	0.414002932	None	None	N
T/V	0.11	likely_benign	0.0913	benign	-0.418	Destabilizing	0.001	N	0.317	neutral	None	None	None	None	N
T/W	0.5859	likely_pathogenic	0.4963	ambiguous	-0.861	Destabilizing	0.985	D	0.639	neutral	None	None	None	None	N
T/Y	0.2406	likely_benign	0.1979	benign	-0.646	Destabilizing	0.851	D	0.592	neutral	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.