TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5646	17161;17162;17163	chr2:178731939;178731938;178731937	chr2:179596666;179596665;179596664
N2AB	5329	16210;16211;16212	chr2:178731939;178731938;178731937	chr2:179596666;179596665;179596664
N2A	4402	13429;13430;13431	chr2:178731939;178731938;178731937	chr2:179596666;179596665;179596664
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: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Ig-40
• Domain position: 10
• Structural Position: 13
• Q(SASA): 0.1369
• 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
I/V	rs753025325	-0.982	None	N	0.075	0.128	0.119812018005	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	5.58E-05	None	0	None	0	0	0
I/V	rs753025325	-0.982	None	N	0.075	0.128	0.119812018005	gnomAD-4.0.0	2.05815E-06	None	None	None	None	N	None	0	0	None	0	2.5264E-05	None	0	0	1.80382E-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
I/A	0.1007	likely_benign	0.1131	benign	-1.651	Destabilizing	None	N	0.125	neutral	None	None	None	None	N
I/C	0.4989	ambiguous	0.5573	ambiguous	-1.009	Destabilizing	0.245	N	0.353	neutral	None	None	None	None	N
I/D	0.4223	ambiguous	0.4883	ambiguous	-1.27	Destabilizing	0.085	N	0.466	neutral	None	None	None	None	N
I/E	0.2541	likely_benign	0.2842	benign	-1.228	Destabilizing	0.018	N	0.352	neutral	None	None	None	None	N
I/F	0.12	likely_benign	0.1405	benign	-1.055	Destabilizing	0.017	N	0.313	neutral	N	0.499197687	None	None	N
I/G	0.3456	ambiguous	0.4076	ambiguous	-2.011	Highly Destabilizing	0.009	N	0.318	neutral	None	None	None	None	N
I/H	0.3337	likely_benign	0.3885	ambiguous	-1.287	Destabilizing	0.245	N	0.421	neutral	None	None	None	None	N
I/K	0.178	likely_benign	0.196	benign	-1.289	Destabilizing	None	N	0.281	neutral	None	None	None	None	N
I/L	0.08	likely_benign	0.0847	benign	-0.716	Destabilizing	None	N	0.053	neutral	N	0.427006727	None	None	N
I/M	0.0624	likely_benign	0.063	benign	-0.597	Destabilizing	0.001	N	0.137	neutral	N	0.450905094	None	None	N
I/N	0.1874	likely_benign	0.2206	benign	-1.169	Destabilizing	0.033	N	0.483	neutral	N	0.493791867	None	None	N
I/P	0.6334	likely_pathogenic	0.7451	pathogenic	-0.997	Destabilizing	0.085	N	0.491	neutral	None	None	None	None	N
I/Q	0.2007	likely_benign	0.2218	benign	-1.269	Destabilizing	0.044	N	0.471	neutral	None	None	None	None	N
I/R	0.1328	likely_benign	0.1498	benign	-0.766	Destabilizing	None	N	0.323	neutral	None	None	None	None	N
I/S	0.1426	likely_benign	0.1614	benign	-1.749	Destabilizing	0.007	N	0.289	neutral	N	0.455926912	None	None	N
I/T	0.069	likely_benign	0.0771	benign	-1.583	Destabilizing	0.007	N	0.327	neutral	N	0.431876616	None	None	N
I/V	0.0555	likely_benign	0.0576	benign	-0.997	Destabilizing	None	N	0.075	neutral	N	0.386714756	None	None	N
I/W	0.5763	likely_pathogenic	0.6641	pathogenic	-1.203	Destabilizing	0.788	D	0.414	neutral	None	None	None	None	N
I/Y	0.3952	ambiguous	0.4444	ambiguous	-0.962	Destabilizing	0.085	N	0.457	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.