TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27050	81373;81374;81375	chr2:178564984;178564983;178564982	chr2:179429711;179429710;179429709
N2AB	25409	76450;76451;76452	chr2:178564984;178564983;178564982	chr2:179429711;179429710;179429709
N2A	24482	73669;73670;73671	chr2:178564984;178564983;178564982	chr2:179429711;179429710;179429709
N2B	17985	54178;54179;54180	chr2:178564984;178564983;178564982	chr2:179429711;179429710;179429709
Novex-1	18110	54553;54554;54555	chr2:178564984;178564983;178564982	chr2:179429711;179429710;179429709
Novex-2	18177	54754;54755;54756	chr2:178564984;178564983;178564982	chr2:179429711;179429710;179429709
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: Fn3-84
• Domain position: 79
• Structural Position: 111
• Q(SASA): 0.2952
• Predicted PPI site: I

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/G	rs938840239	-0.536	1.0	D	0.779	0.615	0.489658423131	gnomAD-2.1.1	4.05E-06	None	None	None	None	I	None	6.48E-05	0	None	0	0	None	0	None	0	0	0
E/G	rs938840239	-0.536	1.0	D	0.779	0.615	0.489658423131	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
E/G	rs938840239	-0.536	1.0	D	0.779	0.615	0.489658423131	gnomAD-4.0.0	2.56751E-06	None	None	None	None	I	None	3.39167E-05	0	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	0.5817	likely_pathogenic	0.5655	pathogenic	-0.89	Destabilizing	0.999	D	0.701	prob.neutral	N	0.477899243	None	None	I
E/C	0.9708	likely_pathogenic	0.9648	pathogenic	-0.552	Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	I
E/D	0.9065	likely_pathogenic	0.8788	pathogenic	-1.436	Destabilizing	0.999	D	0.474	neutral	D	0.522060699	None	None	I
E/F	0.9855	likely_pathogenic	0.9857	pathogenic	-0.983	Destabilizing	1.0	D	0.876	deleterious	None	None	None	None	I
E/G	0.7297	likely_pathogenic	0.7099	pathogenic	-1.223	Destabilizing	1.0	D	0.779	deleterious	D	0.533581588	None	None	I
E/H	0.9592	likely_pathogenic	0.953	pathogenic	-1.204	Destabilizing	1.0	D	0.683	prob.neutral	None	None	None	None	I
E/I	0.856	likely_pathogenic	0.853	pathogenic	0.013	Stabilizing	1.0	D	0.886	deleterious	None	None	None	None	I
E/K	0.7009	likely_pathogenic	0.7032	pathogenic	-0.622	Destabilizing	0.999	D	0.572	neutral	N	0.478254865	None	None	I
E/L	0.9253	likely_pathogenic	0.9269	pathogenic	0.013	Stabilizing	1.0	D	0.864	deleterious	None	None	None	None	I
E/M	0.8465	likely_pathogenic	0.8451	pathogenic	0.554	Stabilizing	1.0	D	0.829	deleterious	None	None	None	None	I
E/N	0.9249	likely_pathogenic	0.9133	pathogenic	-0.981	Destabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	I
E/P	0.9987	likely_pathogenic	0.9986	pathogenic	-0.268	Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	I
E/Q	0.334	likely_benign	0.3288	benign	-0.872	Destabilizing	1.0	D	0.631	neutral	N	0.469429774	None	None	I
E/R	0.8186	likely_pathogenic	0.8284	pathogenic	-0.592	Destabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	I
E/S	0.7457	likely_pathogenic	0.7138	pathogenic	-1.383	Destabilizing	0.999	D	0.621	neutral	None	None	None	None	I
E/T	0.7725	likely_pathogenic	0.7574	pathogenic	-1.08	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	I
E/V	0.6346	likely_pathogenic	0.6366	pathogenic	-0.268	Destabilizing	1.0	D	0.833	deleterious	N	0.479818839	None	None	I
E/W	0.9962	likely_pathogenic	0.9964	pathogenic	-0.975	Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	I
E/Y	0.9814	likely_pathogenic	0.9802	pathogenic	-0.746	Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	I

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.