TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3155	9688;9689;9690	chr2:178767767;178767766;178767765	chr2:179632494;179632493;179632492
N2AB	3155	9688;9689;9690	chr2:178767767;178767766;178767765	chr2:179632494;179632493;179632492
N2A	3155	9688;9689;9690	chr2:178767767;178767766;178767765	chr2:179632494;179632493;179632492
N2B	3109	9550;9551;9552	chr2:178767767;178767766;178767765	chr2:179632494;179632493;179632492
Novex-1	3109	9550;9551;9552	chr2:178767767;178767766;178767765	chr2:179632494;179632493;179632492
Novex-2	3109	9550;9551;9552	chr2:178767767;178767766;178767765	chr2:179632494;179632493;179632492
Novex-3	3155	9688;9689;9690	chr2:178767767;178767766;178767765	chr2:179632494;179632493;179632492

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Ig-22
• Domain position: 9
• Structural Position: 11
• Q(SASA): 0.6248
• 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/Q	rs1458652114	None	0.016	N	0.237	0.084	0.257292322809	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
E/Q	rs1458652114	None	0.016	N	0.237	0.084	0.257292322809	gnomAD-4.0.0	2.02981E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.40982E-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	0.2367	likely_benign	0.2585	benign	-0.717	Destabilizing	0.201	N	0.244	neutral	N	0.502194723	None	None	I
E/C	0.9501	likely_pathogenic	0.9629	pathogenic	-0.506	Destabilizing	0.992	D	0.393	neutral	None	None	None	None	I
E/D	0.1284	likely_benign	0.139	benign	-0.691	Destabilizing	0.004	N	0.084	neutral	N	0.382675332	None	None	I
E/F	0.8659	likely_pathogenic	0.9096	pathogenic	-0.035	Destabilizing	0.92	D	0.389	neutral	None	None	None	None	I
E/G	0.3541	ambiguous	0.3898	ambiguous	-1.035	Destabilizing	0.201	N	0.294	neutral	N	0.511817793	None	None	I
E/H	0.6648	likely_pathogenic	0.7298	pathogenic	0.037	Stabilizing	0.92	D	0.364	neutral	None	None	None	None	I
E/I	0.55	ambiguous	0.6033	pathogenic	0.139	Stabilizing	0.92	D	0.398	neutral	None	None	None	None	I
E/K	0.4076	ambiguous	0.428	ambiguous	-0.291	Destabilizing	0.201	N	0.307	neutral	N	0.496207717	None	None	I
E/L	0.6853	likely_pathogenic	0.7387	pathogenic	0.139	Stabilizing	0.617	D	0.393	neutral	None	None	None	None	I
E/M	0.6362	likely_pathogenic	0.6954	pathogenic	0.279	Stabilizing	0.992	D	0.352	neutral	None	None	None	None	I
E/N	0.3135	likely_benign	0.3341	benign	-0.862	Destabilizing	0.021	N	0.236	neutral	None	None	None	None	I
E/P	0.8769	likely_pathogenic	0.8487	pathogenic	-0.126	Destabilizing	0.92	D	0.361	neutral	None	None	None	None	I
E/Q	0.2859	likely_benign	0.3051	benign	-0.736	Destabilizing	0.016	N	0.237	neutral	N	0.497479576	None	None	I
E/R	0.5762	likely_pathogenic	0.604	pathogenic	0.124	Stabilizing	0.447	N	0.34	neutral	None	None	None	None	I
E/S	0.297	likely_benign	0.334	benign	-1.097	Destabilizing	0.021	N	0.132	neutral	None	None	None	None	I
E/T	0.2964	likely_benign	0.3238	benign	-0.826	Destabilizing	0.447	N	0.281	neutral	None	None	None	None	I
E/V	0.318	likely_benign	0.3579	ambiguous	-0.126	Destabilizing	0.549	D	0.374	neutral	N	0.503721528	None	None	I
E/W	0.9527	likely_pathogenic	0.9692	pathogenic	0.281	Stabilizing	0.992	D	0.51	neutral	None	None	None	None	I
E/Y	0.7772	likely_pathogenic	0.8343	pathogenic	0.231	Stabilizing	0.972	D	0.382	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.