TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19888	59887;59888;59889	chr2:178592242;178592241;178592240	chr2:179456969;179456968;179456967
N2AB	18247	54964;54965;54966	chr2:178592242;178592241;178592240	chr2:179456969;179456968;179456967
N2A	17320	52183;52184;52185	chr2:178592242;178592241;178592240	chr2:179456969;179456968;179456967
N2B	10823	32692;32693;32694	chr2:178592242;178592241;178592240	chr2:179456969;179456968;179456967
Novex-1	10948	33067;33068;33069	chr2:178592242;178592241;178592240	chr2:179456969;179456968;179456967
Novex-2	11015	33268;33269;33270	chr2:178592242;178592241;178592240	chr2:179456969;179456968;179456967
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-32
• Domain position: 12
• Structural Position: 14
• Q(SASA): 0.2679
• 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/A	rs564006895	-0.89	0.896	D	0.558	0.403	0.365509141856	gnomAD-2.1.1	1.64E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.83E-05	3.37268E-04
E/A	rs564006895	-0.89	0.896	D	0.558	0.403	0.365509141856	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	6.55E-05	0	0	0	None	0	0	0	0	0
E/A	rs564006895	-0.89	0.896	D	0.558	0.403	0.365509141856	1000 genomes	1.99681E-04	None	None	None	None	N	None	0	1.4E-03	None	None	0	0	None	None	None	0	None
E/A	rs564006895	-0.89	0.896	D	0.558	0.403	0.365509141856	gnomAD-4.0.0	1.42704E-05	None	None	None	None	N	None	0	1.6733E-05	None	0	0	None	1.56647E-05	0	1.78131E-05	0	0
E/K	rs369279578	0.227	0.896	N	0.533	0.345	None	gnomAD-2.1.1	1.23E-05	None	None	None	None	N	None	0	0	None	0	0	None	3.31E-05	None	0	1.83E-05	0
E/K	rs369279578	0.227	0.896	N	0.533	0.345	None	gnomAD-4.0.0	6.85213E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.10174E-06	1.16344E-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
E/A	0.49	ambiguous	0.4859	ambiguous	-0.453	Destabilizing	0.896	D	0.558	neutral	D	0.523887409	None	None	N
E/C	0.9633	likely_pathogenic	0.9604	pathogenic	-0.348	Destabilizing	0.999	D	0.713	prob.delet.	None	None	None	None	N
E/D	0.1856	likely_benign	0.1576	benign	-0.543	Destabilizing	0.004	N	0.116	neutral	N	0.426128788	None	None	N
E/F	0.9487	likely_pathogenic	0.9489	pathogenic	0.24	Stabilizing	0.996	D	0.687	prob.neutral	None	None	None	None	N
E/G	0.5062	ambiguous	0.5035	ambiguous	-0.749	Destabilizing	0.896	D	0.582	neutral	N	0.468027876	None	None	N
E/H	0.8214	likely_pathogenic	0.8218	pathogenic	0.519	Stabilizing	0.996	D	0.553	neutral	None	None	None	None	N
E/I	0.8301	likely_pathogenic	0.8262	pathogenic	0.331	Stabilizing	0.988	D	0.684	prob.neutral	None	None	None	None	N
E/K	0.603	likely_pathogenic	0.6025	pathogenic	0.248	Stabilizing	0.896	D	0.533	neutral	N	0.518905663	None	None	N
E/L	0.8418	likely_pathogenic	0.8356	pathogenic	0.331	Stabilizing	0.988	D	0.657	neutral	None	None	None	None	N
E/M	0.8248	likely_pathogenic	0.8228	pathogenic	0.331	Stabilizing	0.999	D	0.639	neutral	None	None	None	None	N
E/N	0.5123	ambiguous	0.4864	ambiguous	-0.559	Destabilizing	0.851	D	0.521	neutral	None	None	None	None	N
E/P	0.9742	likely_pathogenic	0.9707	pathogenic	0.09	Stabilizing	0.988	D	0.579	neutral	None	None	None	None	N
E/Q	0.3855	ambiguous	0.3911	ambiguous	-0.416	Destabilizing	0.946	D	0.536	neutral	N	0.473485606	None	None	N
E/R	0.7417	likely_pathogenic	0.744	pathogenic	0.633	Stabilizing	0.988	D	0.557	neutral	None	None	None	None	N
E/S	0.516	ambiguous	0.5042	ambiguous	-0.706	Destabilizing	0.919	D	0.509	neutral	None	None	None	None	N
E/T	0.6442	likely_pathogenic	0.6355	pathogenic	-0.432	Destabilizing	0.959	D	0.568	neutral	None	None	None	None	N
E/V	0.6658	likely_pathogenic	0.6636	pathogenic	0.09	Stabilizing	0.984	D	0.583	neutral	N	0.483689823	None	None	N
E/W	0.9831	likely_pathogenic	0.9814	pathogenic	0.564	Stabilizing	0.999	D	0.717	prob.delet.	None	None	None	None	N
E/Y	0.8948	likely_pathogenic	0.8887	pathogenic	0.54	Stabilizing	0.996	D	0.664	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.