TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15814	47665;47666;47667	chr2:178617911;178617910;178617909	chr2:179482638;179482637;179482636
N2AB	14173	42742;42743;42744	chr2:178617911;178617910;178617909	chr2:179482638;179482637;179482636
N2A	13246	39961;39962;39963	chr2:178617911;178617910;178617909	chr2:179482638;179482637;179482636
N2B	6749	20470;20471;20472	chr2:178617911;178617910;178617909	chr2:179482638;179482637;179482636
Novex-1	6874	20845;20846;20847	chr2:178617911;178617910;178617909	chr2:179482638;179482637;179482636
Novex-2	6941	21046;21047;21048	chr2:178617911;178617910;178617909	chr2:179482638;179482637;179482636
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: Fn3-2
• Domain position: 57
• Structural Position: 83
• Q(SASA): 0.6012
• 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	rs769902441	0.522	0.183	N	0.178	0.165	0.253726318573	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.91E-06	0
E/K	rs769902441	0.522	0.183	N	0.178	0.165	0.253726318573	gnomAD-4.0.0	3.18681E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.72577E-06	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	0.1152	likely_benign	0.1239	benign	-0.299	Destabilizing	0.101	N	0.215	neutral	N	0.477419937	None	None	N
E/C	0.7051	likely_pathogenic	0.7119	pathogenic	-0.221	Destabilizing	0.983	D	0.212	neutral	None	None	None	None	N
E/D	0.0993	likely_benign	0.1007	benign	-0.336	Destabilizing	None	N	0.052	neutral	N	0.416455954	None	None	N
E/F	0.6765	likely_pathogenic	0.6705	pathogenic	-0.176	Destabilizing	0.836	D	0.267	neutral	None	None	None	None	N
E/G	0.088	likely_benign	0.097	benign	-0.474	Destabilizing	0.001	N	0.131	neutral	N	0.481676166	None	None	N
E/H	0.3165	likely_benign	0.3327	benign	0.286	Stabilizing	0.001	N	0.083	neutral	None	None	None	None	N
E/I	0.3941	ambiguous	0.3894	ambiguous	0.124	Stabilizing	0.836	D	0.301	neutral	None	None	None	None	N
E/K	0.1003	likely_benign	0.11	benign	0.268	Stabilizing	0.183	N	0.178	neutral	N	0.441491405	None	None	N
E/L	0.3968	ambiguous	0.4006	ambiguous	0.124	Stabilizing	0.418	N	0.346	neutral	None	None	None	None	N
E/M	0.4394	ambiguous	0.4493	ambiguous	0.03	Stabilizing	0.94	D	0.232	neutral	None	None	None	None	N
E/N	0.1616	likely_benign	0.1639	benign	-0.057	Destabilizing	0.004	N	0.099	neutral	None	None	None	None	N
E/P	0.439	ambiguous	0.4421	ambiguous	0.003	Stabilizing	0.593	D	0.357	neutral	None	None	None	None	N
E/Q	0.1142	likely_benign	0.1222	benign	-0.026	Destabilizing	0.351	N	0.269	neutral	N	0.483835244	None	None	N
E/R	0.1585	likely_benign	0.1707	benign	0.575	Stabilizing	0.418	N	0.219	neutral	None	None	None	None	N
E/S	0.1194	likely_benign	0.1236	benign	-0.218	Destabilizing	0.228	N	0.153	neutral	None	None	None	None	N
E/T	0.1539	likely_benign	0.1578	benign	-0.073	Destabilizing	0.418	N	0.269	neutral	None	None	None	None	N
E/V	0.2316	likely_benign	0.2283	benign	0.003	Stabilizing	0.523	D	0.363	neutral	N	0.48758331	None	None	N
E/W	0.7678	likely_pathogenic	0.7941	pathogenic	-0.041	Destabilizing	0.983	D	0.205	neutral	None	None	None	None	N
E/Y	0.5287	ambiguous	0.5365	ambiguous	0.062	Stabilizing	0.716	D	0.334	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.