TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9780	29563;29564;29565	chr2:178706536;178706535;178706534	chr2:179571263;179571262;179571261
N2AB	9463	28612;28613;28614	chr2:178706536;178706535;178706534	chr2:179571263;179571262;179571261
N2A	8536	25831;25832;25833	chr2:178706536;178706535;178706534	chr2:179571263;179571262;179571261
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-83
• Domain position: 83
• Structural Position: 166
• Q(SASA): 0.1039
• 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
I/F	rs916661752	None	0.982	None	0.617	0.408	0.460526725402	gnomAD-4.0.0	3.18216E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	5.71585E-06	0	0
I/T	None	None	0.939	None	0.635	0.343	0.625546071808	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	0	3.66327E-05

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	0.743	likely_pathogenic	0.5631	ambiguous	-1.654	Destabilizing	0.91	D	0.571	neutral	None	None	None	None	I
I/C	0.9687	likely_pathogenic	0.9389	pathogenic	-0.979	Destabilizing	0.999	D	0.656	neutral	None	None	None	None	I
I/D	0.9827	likely_pathogenic	0.9433	pathogenic	-1.201	Destabilizing	0.998	D	0.767	deleterious	None	None	None	None	I
I/E	0.9327	likely_pathogenic	0.8522	pathogenic	-1.103	Destabilizing	0.993	D	0.765	deleterious	None	None	None	None	I
I/F	0.6191	likely_pathogenic	0.4628	ambiguous	-0.911	Destabilizing	0.982	D	0.617	neutral	None	None	None	None	I
I/G	0.9737	likely_pathogenic	0.9339	pathogenic	-2.056	Highly Destabilizing	0.993	D	0.747	deleterious	None	None	None	None	I
I/H	0.9647	likely_pathogenic	0.9104	pathogenic	-1.198	Destabilizing	0.999	D	0.755	deleterious	None	None	None	None	I
I/K	0.8146	likely_pathogenic	0.7096	pathogenic	-1.162	Destabilizing	0.993	D	0.765	deleterious	None	None	None	None	I
I/L	0.3853	ambiguous	0.2995	benign	-0.581	Destabilizing	0.58	D	0.408	neutral	None	None	None	None	I
I/M	0.2237	likely_benign	0.1563	benign	-0.529	Destabilizing	0.991	D	0.607	neutral	None	None	None	None	I
I/N	0.8609	likely_pathogenic	0.7311	pathogenic	-1.216	Destabilizing	0.997	D	0.769	deleterious	None	None	None	None	I
I/P	0.9962	likely_pathogenic	0.9901	pathogenic	-0.91	Destabilizing	0.998	D	0.772	deleterious	None	None	None	None	I
I/Q	0.9014	likely_pathogenic	0.8035	pathogenic	-1.25	Destabilizing	0.998	D	0.761	deleterious	None	None	None	None	I
I/R	0.7689	likely_pathogenic	0.6222	pathogenic	-0.701	Destabilizing	0.993	D	0.766	deleterious	None	None	None	None	I
I/S	0.8247	likely_pathogenic	0.6534	pathogenic	-1.871	Destabilizing	0.991	D	0.675	prob.neutral	None	None	None	None	I
I/T	0.4621	ambiguous	0.2797	benign	-1.644	Destabilizing	0.939	D	0.635	neutral	None	None	None	None	I
I/V	0.1723	likely_benign	0.1376	benign	-0.91	Destabilizing	0.02	N	0.213	neutral	None	None	None	None	I
I/W	0.9644	likely_pathogenic	0.9223	pathogenic	-1.097	Destabilizing	0.999	D	0.715	prob.delet.	None	None	None	None	I
I/Y	0.9189	likely_pathogenic	0.8562	pathogenic	-0.81	Destabilizing	0.993	D	0.679	prob.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.