TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5781	17566;17567;17568	chr2:178731425;178731424;178731423	chr2:179596152;179596151;179596150
N2AB	5464	16615;16616;16617	chr2:178731425;178731424;178731423	chr2:179596152;179596151;179596150
N2A	4537	13834;13835;13836	chr2:178731425;178731424;178731423	chr2:179596152;179596151;179596150
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-41
• Domain position: 52
• Structural Position: 130
• Q(SASA): 0.7308
• 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	rs1414405507	-0.312	0.801	N	0.434	0.361	0.42573502686	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.88E-06	0
E/K	rs1400453149	0.815	0.005	N	0.124	0.246	0.236890367714	gnomAD-2.1.1	3.19E-05	None	None	None	None	I	None	0	0	None	0	6.4433E-04	None	0	None	0	0	0
E/K	rs1400453149	0.815	0.005	N	0.124	0.246	0.236890367714	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	1.93125E-04	None	0	0	0	0	0
E/K	rs1400453149	0.815	0.005	N	0.124	0.246	0.236890367714	gnomAD-4.0.0	6.5741E-06	None	None	None	None	I	None	0	0	None	0	1.93125E-04	None	0	0	0	0	0
E/Q	None	None	0.801	D	0.343	0.168	0.283761946502	gnomAD-4.0.0	1.59125E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85814E-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	0.199	likely_benign	0.1951	benign	-0.5	Destabilizing	0.454	N	0.384	neutral	D	0.526672289	None	None	I
E/C	0.8348	likely_pathogenic	0.8158	pathogenic	-0.229	Destabilizing	0.998	D	0.41	neutral	None	None	None	None	I
E/D	0.1476	likely_benign	0.1504	benign	-0.315	Destabilizing	0.801	D	0.347	neutral	N	0.500755125	None	None	I
E/F	0.7327	likely_pathogenic	0.7167	pathogenic	-0.218	Destabilizing	0.949	D	0.389	neutral	None	None	None	None	I
E/G	0.2229	likely_benign	0.2195	benign	-0.701	Destabilizing	0.801	D	0.434	neutral	N	0.485798596	None	None	I
E/H	0.3848	ambiguous	0.3706	ambiguous	0.125	Stabilizing	0.991	D	0.289	neutral	None	None	None	None	I
E/I	0.3222	likely_benign	0.3008	benign	0.001	Stabilizing	0.728	D	0.387	neutral	None	None	None	None	I
E/K	0.1427	likely_benign	0.1341	benign	0.283	Stabilizing	0.005	N	0.124	neutral	N	0.501139127	None	None	I
E/L	0.4097	ambiguous	0.3912	ambiguous	0.001	Stabilizing	0.728	D	0.415	neutral	None	None	None	None	I
E/M	0.4723	ambiguous	0.4533	ambiguous	0.033	Stabilizing	0.974	D	0.389	neutral	None	None	None	None	I
E/N	0.2736	likely_benign	0.2721	benign	-0.199	Destabilizing	0.842	D	0.31	neutral	None	None	None	None	I
E/P	0.9204	likely_pathogenic	0.9131	pathogenic	-0.147	Destabilizing	0.974	D	0.333	neutral	None	None	None	None	I
E/Q	0.1116	likely_benign	0.1077	benign	-0.132	Destabilizing	0.801	D	0.343	neutral	D	0.526672289	None	None	I
E/R	0.2149	likely_benign	0.2062	benign	0.554	Stabilizing	0.728	D	0.339	neutral	None	None	None	None	I
E/S	0.2198	likely_benign	0.2168	benign	-0.334	Destabilizing	0.842	D	0.342	neutral	None	None	None	None	I
E/T	0.239	likely_benign	0.2247	benign	-0.156	Destabilizing	0.842	D	0.353	neutral	None	None	None	None	I
E/V	0.2064	likely_benign	0.1932	benign	-0.147	Destabilizing	0.012	N	0.268	neutral	N	0.505566299	None	None	I
E/W	0.8567	likely_pathogenic	0.8475	pathogenic	-0.002	Destabilizing	0.998	D	0.496	neutral	None	None	None	None	I
E/Y	0.5843	likely_pathogenic	0.576	pathogenic	0.035	Stabilizing	0.974	D	0.393	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.