TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26160	78703;78704;78705	chr2:178567654;178567653;178567652	chr2:179432381;179432380;179432379
N2AB	24519	73780;73781;73782	chr2:178567654;178567653;178567652	chr2:179432381;179432380;179432379
N2A	23592	70999;71000;71001	chr2:178567654;178567653;178567652	chr2:179432381;179432380;179432379
N2B	17095	51508;51509;51510	chr2:178567654;178567653;178567652	chr2:179432381;179432380;179432379
Novex-1	17220	51883;51884;51885	chr2:178567654;178567653;178567652	chr2:179432381;179432380;179432379
Novex-2	17287	52084;52085;52086	chr2:178567654;178567653;178567652	chr2:179432381;179432380;179432379
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: Fn3-78
• Domain position: 73
• Structural Position: 105
• Q(SASA): 0.1947
• 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	None	None	0.896	N	0.689	0.491	0.408172294925	gnomAD-4.0.0	1.20033E-06	None	None	None	None	N	None	0	1.01626E-03	None	0	0	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
E/A	0.6212	likely_pathogenic	0.5676	pathogenic	-0.928	Destabilizing	0.896	D	0.689	prob.neutral	N	0.483120391	None	None	N
E/C	0.958	likely_pathogenic	0.9482	pathogenic	-0.13	Destabilizing	0.999	D	0.79	deleterious	None	None	None	None	N
E/D	0.508	ambiguous	0.3765	ambiguous	-1.345	Destabilizing	0.004	N	0.306	neutral	N	0.509094101	None	None	N
E/F	0.9849	likely_pathogenic	0.9773	pathogenic	-0.512	Destabilizing	0.996	D	0.804	deleterious	None	None	None	None	N
E/G	0.8652	likely_pathogenic	0.8271	pathogenic	-1.37	Destabilizing	0.896	D	0.69	prob.neutral	N	0.521988701	None	None	N
E/H	0.9347	likely_pathogenic	0.903	pathogenic	-0.462	Destabilizing	0.996	D	0.669	neutral	None	None	None	None	N
E/I	0.8815	likely_pathogenic	0.8367	pathogenic	0.336	Stabilizing	0.988	D	0.795	deleterious	None	None	None	None	N
E/K	0.8861	likely_pathogenic	0.8425	pathogenic	-0.684	Destabilizing	0.896	D	0.692	prob.neutral	N	0.518750948	None	None	N
E/L	0.9421	likely_pathogenic	0.9123	pathogenic	0.336	Stabilizing	0.988	D	0.75	deleterious	None	None	None	None	N
E/M	0.9178	likely_pathogenic	0.8788	pathogenic	1.024	Stabilizing	0.999	D	0.759	deleterious	None	None	None	None	N
E/N	0.8485	likely_pathogenic	0.7796	pathogenic	-1.088	Destabilizing	0.851	D	0.673	neutral	None	None	None	None	N
E/P	0.9984	likely_pathogenic	0.998	pathogenic	-0.068	Destabilizing	0.988	D	0.699	prob.neutral	None	None	None	None	N
E/Q	0.5004	ambiguous	0.4491	ambiguous	-0.746	Destabilizing	0.946	D	0.661	neutral	N	0.473672019	None	None	N
E/R	0.9118	likely_pathogenic	0.8833	pathogenic	-0.67	Destabilizing	0.988	D	0.653	neutral	None	None	None	None	N
E/S	0.6835	likely_pathogenic	0.6198	pathogenic	-1.725	Destabilizing	0.919	D	0.689	prob.neutral	None	None	None	None	N
E/T	0.8388	likely_pathogenic	0.7853	pathogenic	-1.294	Destabilizing	0.959	D	0.687	prob.neutral	None	None	None	None	N
E/V	0.7658	likely_pathogenic	0.6876	pathogenic	-0.068	Destabilizing	0.984	D	0.703	prob.neutral	N	0.469927207	None	None	N
E/W	0.995	likely_pathogenic	0.9928	pathogenic	-0.569	Destabilizing	0.999	D	0.747	deleterious	None	None	None	None	N
E/Y	0.9678	likely_pathogenic	0.9539	pathogenic	-0.259	Destabilizing	0.996	D	0.761	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.