TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33660	101203;101204;101205	chr2:178535637;178535636;178535635	chr2:179400364;179400363;179400362
N2AB	32019	96280;96281;96282	chr2:178535637;178535636;178535635	chr2:179400364;179400363;179400362
N2A	31092	93499;93500;93501	chr2:178535637;178535636;178535635	chr2:179400364;179400363;179400362
N2B	24595	74008;74009;74010	chr2:178535637;178535636;178535635	chr2:179400364;179400363;179400362
Novex-1	24720	74383;74384;74385	chr2:178535637;178535636;178535635	chr2:179400364;179400363;179400362
Novex-2	24787	74584;74585;74586	chr2:178535637;178535636;178535635	chr2:179400364;179400363;179400362
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-159
• Domain position: 65
• Structural Position: 145
• Q(SASA): 0.2785
• 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/D	rs727503536	None	0.002	N	0.233	0.064	0.260249123532	gnomAD-4.0.0	2.05268E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79895E-06	0	1.65651E-05
E/G	rs1309484886	-1.067	0.932	N	0.436	0.49	0.56713362702	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.9E-06	0
E/G	rs1309484886	-1.067	0.932	N	0.436	0.49	0.56713362702	gnomAD-4.0.0	6.84207E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99467E-07	0	0
E/K	rs1355308623	-0.304	0.791	N	0.423	0.288	0.400613892164	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
E/K	rs1355308623	-0.304	0.791	N	0.423	0.288	0.400613892164	gnomAD-4.0.0	1.59129E-06	None	None	None	None	N	None	0	2.28634E-05	None	0	0	None	0	0	0	0	0
E/Q	None	None	0.174	N	0.233	0.161	0.266385636622	gnomAD-4.0.0	1.59129E-06	None	None	None	None	N	None	0	2.28634E-05	None	0	0	None	0	0	0	0	0
E/V	rs1309484886	0.285	0.947	N	0.497	0.557	0.681466305809	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.9E-06	0
E/V	rs1309484886	0.285	0.947	N	0.497	0.557	0.681466305809	gnomAD-4.0.0	4.78945E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	6.29627E-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	0.3259	likely_benign	0.2337	benign	-0.615	Destabilizing	0.804	D	0.398	neutral	N	0.492655716	None	None	N
E/C	0.9443	likely_pathogenic	0.8875	pathogenic	-0.359	Destabilizing	0.998	D	0.711	prob.delet.	None	None	None	None	N
E/D	0.1239	likely_benign	0.1236	benign	-0.903	Destabilizing	0.002	N	0.233	neutral	N	0.483132156	None	None	N
E/F	0.9242	likely_pathogenic	0.8432	pathogenic	-0.066	Destabilizing	0.999	D	0.647	neutral	None	None	None	None	N
E/G	0.3066	likely_benign	0.1986	benign	-0.95	Destabilizing	0.932	D	0.436	neutral	N	0.50941468	None	None	N
E/H	0.7583	likely_pathogenic	0.5969	pathogenic	-0.212	Destabilizing	0.981	D	0.396	neutral	None	None	None	None	N
E/I	0.764	likely_pathogenic	0.626	pathogenic	0.283	Stabilizing	0.971	D	0.654	neutral	None	None	None	None	N
E/K	0.4966	ambiguous	0.2955	benign	-0.386	Destabilizing	0.791	D	0.423	neutral	N	0.46746927	None	None	N
E/L	0.6413	likely_pathogenic	0.4689	ambiguous	0.283	Stabilizing	0.943	D	0.553	neutral	None	None	None	None	N
E/M	0.7472	likely_pathogenic	0.614	pathogenic	0.542	Stabilizing	0.986	D	0.591	neutral	None	None	None	None	N
E/N	0.3476	ambiguous	0.268	benign	-0.848	Destabilizing	0.793	D	0.392	neutral	None	None	None	None	N
E/P	0.9486	likely_pathogenic	0.8902	pathogenic	0.005	Stabilizing	0.833	D	0.463	neutral	None	None	None	None	N
E/Q	0.28	likely_benign	0.1867	benign	-0.715	Destabilizing	0.174	N	0.233	neutral	N	0.432529977	None	None	N
E/R	0.6324	likely_pathogenic	0.4314	ambiguous	-0.068	Destabilizing	0.972	D	0.405	neutral	None	None	None	None	N
E/S	0.3013	likely_benign	0.2198	benign	-1.09	Destabilizing	0.844	D	0.377	neutral	None	None	None	None	N
E/T	0.4203	ambiguous	0.3125	benign	-0.815	Destabilizing	0.963	D	0.395	neutral	None	None	None	None	N
E/V	0.5129	ambiguous	0.384	ambiguous	0.005	Stabilizing	0.947	D	0.497	neutral	N	0.504912938	None	None	N
E/W	0.9797	likely_pathogenic	0.9487	pathogenic	0.169	Stabilizing	1.0	D	0.705	prob.neutral	None	None	None	None	N
E/Y	0.8832	likely_pathogenic	0.765	pathogenic	0.176	Stabilizing	0.998	D	0.593	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.