TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6773	20542;20543;20544	chr2:178726005;178726004;178726003	chr2:179590732;179590731;179590730
N2AB	6456	19591;19592;19593	chr2:178726005;178726004;178726003	chr2:179590732;179590731;179590730
N2A	5529	16810;16811;16812	chr2:178726005;178726004;178726003	chr2:179590732;179590731;179590730
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: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Ig-52
• Domain position: 13
• Structural Position: 18
• Q(SASA): 0.6468
• 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
L/F	rs189557659	-0.62	0.925	N	0.457	0.299	None	gnomAD-3.1.2	1.97E-05	None	None	None	None	I	None	0	0	0	0	5.80271E-04	None	0	0	0	0	0
L/F	rs189557659	-0.62	0.925	N	0.457	0.299	None	1000 genomes	1.99681E-04	None	None	None	None	I	None	0	0	None	None	1E-03	0	None	None	None	0	None
L/F	rs189557659	-0.62	0.925	N	0.457	0.299	None	gnomAD-4.0.0	3.28221E-05	None	None	None	None	I	None	0	0	None	0	1.16449E-03	None	0	0	0	0	1.63372E-05
L/P	rs1327286420	-0.657	0.99	D	0.641	0.557	0.789426192391	gnomAD-4.0.0	1.64061E-06	None	None	None	None	I	None	0	0	None	0	2.82917E-05	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
L/A	0.1933	likely_benign	0.1719	benign	-0.946	Destabilizing	0.743	D	0.495	neutral	None	None	None	None	I
L/C	0.547	ambiguous	0.5186	ambiguous	-0.689	Destabilizing	0.998	D	0.515	neutral	None	None	None	None	I
L/D	0.5826	likely_pathogenic	0.5636	ambiguous	-0.255	Destabilizing	0.992	D	0.64	neutral	None	None	None	None	I
L/E	0.2743	likely_benign	0.2731	benign	-0.31	Destabilizing	0.968	D	0.645	neutral	None	None	None	None	I
L/F	0.1339	likely_benign	0.1131	benign	-0.719	Destabilizing	0.925	D	0.457	neutral	N	0.492391507	None	None	I
L/G	0.3945	ambiguous	0.3675	ambiguous	-1.179	Destabilizing	0.976	D	0.639	neutral	None	None	None	None	I
L/H	0.241	likely_benign	0.2165	benign	-0.379	Destabilizing	0.993	D	0.673	neutral	N	0.507431116	None	None	I
L/I	0.095	likely_benign	0.0829	benign	-0.429	Destabilizing	0.002	N	0.218	neutral	N	0.516319223	None	None	I
L/K	0.227	likely_benign	0.2224	benign	-0.572	Destabilizing	0.547	D	0.615	neutral	None	None	None	None	I
L/M	0.1131	likely_benign	0.1016	benign	-0.424	Destabilizing	0.831	D	0.444	neutral	None	None	None	None	I
L/N	0.2985	likely_benign	0.2642	benign	-0.352	Destabilizing	0.992	D	0.642	neutral	None	None	None	None	I
L/P	0.2704	likely_benign	0.2623	benign	-0.567	Destabilizing	0.99	D	0.641	neutral	D	0.532019394	None	None	I
L/Q	0.1181	likely_benign	0.1102	benign	-0.547	Destabilizing	0.981	D	0.611	neutral	None	None	None	None	I
L/R	0.1853	likely_benign	0.1886	benign	-0.006	Destabilizing	0.974	D	0.614	neutral	N	0.484302805	None	None	I
L/S	0.1819	likely_benign	0.1641	benign	-0.897	Destabilizing	0.976	D	0.578	neutral	None	None	None	None	I
L/T	0.1683	likely_benign	0.1514	benign	-0.836	Destabilizing	0.634	D	0.497	neutral	None	None	None	None	I
L/V	0.0883	likely_benign	0.0808	benign	-0.567	Destabilizing	None	N	0.221	neutral	N	0.466757194	None	None	I
L/W	0.2515	likely_benign	0.248	benign	-0.739	Destabilizing	0.999	D	0.679	prob.neutral	None	None	None	None	I
L/Y	0.3513	ambiguous	0.3197	benign	-0.507	Destabilizing	0.854	D	0.474	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.