TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4895	14908;14909;14910	chr2:178735763;178735762;178735761	chr2:179600490;179600489;179600488
N2AB	4578	13957;13958;13959	chr2:178735763;178735762;178735761	chr2:179600490;179600489;179600488
N2A	3651	11176;11177;11178	chr2:178735763;178735762;178735761	chr2:179600490;179600489;179600488
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: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Ig-32
• Domain position: 8
• Structural Position: 9
• Q(SASA): 0.8143
• 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	rs753337029	-0.02	None	D	0.215	0.117	0.404733080969	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
E/G	rs753337029	-0.02	None	D	0.215	0.117	0.404733080969	gnomAD-4.0.0	1.5915E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.43283E-05	0
E/Q	None	None	0.001	N	0.158	0.113	0.236278675362	gnomAD-4.0.0	1.36851E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.79893E-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	0.1224	likely_benign	0.0983	benign	-0.094	Destabilizing	0.012	N	0.362	neutral	N	0.510566834	None	None	I
E/C	0.7441	likely_pathogenic	0.6175	pathogenic	-0.25	Destabilizing	0.676	D	0.392	neutral	None	None	None	None	I
E/D	0.129	likely_benign	0.1062	benign	-0.295	Destabilizing	None	N	0.118	neutral	D	0.541492705	None	None	I
E/F	0.5665	likely_pathogenic	0.4635	ambiguous	-0.035	Destabilizing	0.214	N	0.453	neutral	None	None	None	None	I
E/G	0.1169	likely_benign	0.0963	benign	-0.245	Destabilizing	None	N	0.215	neutral	D	0.531237564	None	None	I
E/H	0.35	ambiguous	0.2613	benign	0.526	Stabilizing	0.356	N	0.391	neutral	None	None	None	None	I
E/I	0.2378	likely_benign	0.182	benign	0.254	Stabilizing	0.013	N	0.526	neutral	None	None	None	None	I
E/K	0.1035	likely_benign	0.0838	benign	0.336	Stabilizing	0.029	N	0.348	neutral	N	0.391502276	None	None	I
E/L	0.229	likely_benign	0.1731	benign	0.254	Stabilizing	0.038	N	0.461	neutral	None	None	None	None	I
E/M	0.3249	likely_benign	0.2496	benign	0.006	Stabilizing	0.214	N	0.423	neutral	None	None	None	None	I
E/N	0.2072	likely_benign	0.1513	benign	0.062	Stabilizing	0.038	N	0.332	neutral	None	None	None	None	I
E/P	0.4483	ambiguous	0.3584	ambiguous	0.157	Stabilizing	0.356	N	0.437	neutral	None	None	None	None	I
E/Q	0.0997	likely_benign	0.0852	benign	0.084	Stabilizing	0.001	N	0.158	neutral	N	0.473657261	None	None	I
E/R	0.1869	likely_benign	0.1487	benign	0.64	Stabilizing	0.038	N	0.381	neutral	None	None	None	None	I
E/S	0.1507	likely_benign	0.1204	benign	-0.096	Destabilizing	0.016	N	0.314	neutral	None	None	None	None	I
E/T	0.1653	likely_benign	0.1286	benign	0.031	Stabilizing	0.072	N	0.432	neutral	None	None	None	None	I
E/V	0.1421	likely_benign	0.1158	benign	0.157	Stabilizing	None	N	0.196	neutral	N	0.502095653	None	None	I
E/W	0.8168	likely_pathogenic	0.7096	pathogenic	0.051	Stabilizing	0.864	D	0.412	neutral	None	None	None	None	I
E/Y	0.4613	ambiguous	0.3545	ambiguous	0.197	Stabilizing	0.356	N	0.454	neutral	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.