TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21146	63661;63662;63663	chr2:178587971;178587970;178587969	chr2:179452698;179452697;179452696
N2AB	19505	58738;58739;58740	chr2:178587971;178587970;178587969	chr2:179452698;179452697;179452696
N2A	18578	55957;55958;55959	chr2:178587971;178587970;178587969	chr2:179452698;179452697;179452696
N2B	12081	36466;36467;36468	chr2:178587971;178587970;178587969	chr2:179452698;179452697;179452696
Novex-1	12206	36841;36842;36843	chr2:178587971;178587970;178587969	chr2:179452698;179452697;179452696
Novex-2	12273	37042;37043;37044	chr2:178587971;178587970;178587969	chr2:179452698;179452697;179452696
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: C
• RefSeq wild type transcript codon: TGT
• RefSeq wild type template codon: ACA
• Domain: Fn3-41
• Domain position: 83
• Structural Position: 109
• Q(SASA): 0.1042
• 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
C/Y	rs373360112	-1.355	0.975	N	0.741	0.325	None	gnomAD-2.1.1	1.22E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	2.7E-05	0
C/Y	rs373360112	-1.355	0.975	N	0.741	0.325	None	gnomAD-4.0.0	4.11121E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.60081E-06	0	3.31862E-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
C/A	0.3148	likely_benign	0.3196	benign	-1.656	Destabilizing	0.085	N	0.459	neutral	None	None	None	None	N
C/D	0.8719	likely_pathogenic	0.8697	pathogenic	-1.818	Destabilizing	0.495	N	0.695	prob.neutral	None	None	None	None	N
C/E	0.8852	likely_pathogenic	0.8834	pathogenic	-1.599	Destabilizing	0.704	D	0.707	prob.neutral	None	None	None	None	N
C/F	0.225	likely_benign	0.2143	benign	-1.034	Destabilizing	0.975	D	0.741	deleterious	N	0.433708121	None	None	N
C/G	0.288	likely_benign	0.2873	benign	-1.976	Destabilizing	0.27	N	0.717	prob.delet.	N	0.51109147	None	None	N
C/H	0.5458	ambiguous	0.5394	ambiguous	-2.245	Highly Destabilizing	0.981	D	0.726	prob.delet.	None	None	None	None	N
C/I	0.5825	likely_pathogenic	0.5541	ambiguous	-0.794	Destabilizing	0.828	D	0.719	prob.delet.	None	None	None	None	N
C/K	0.8391	likely_pathogenic	0.8469	pathogenic	-1.497	Destabilizing	0.495	N	0.693	prob.neutral	None	None	None	None	N
C/L	0.4493	ambiguous	0.4512	ambiguous	-0.794	Destabilizing	0.495	N	0.666	neutral	None	None	None	None	N
C/M	0.5309	ambiguous	0.521	ambiguous	-0.392	Destabilizing	0.981	D	0.72	prob.delet.	None	None	None	None	N
C/N	0.6045	likely_pathogenic	0.5949	pathogenic	-1.978	Destabilizing	0.704	D	0.712	prob.delet.	None	None	None	None	N
C/P	0.9946	likely_pathogenic	0.9954	pathogenic	-1.061	Destabilizing	0.828	D	0.741	deleterious	None	None	None	None	N
C/Q	0.6434	likely_pathogenic	0.6461	pathogenic	-1.532	Destabilizing	0.828	D	0.741	deleterious	None	None	None	None	N
C/R	0.5224	ambiguous	0.5254	ambiguous	-1.829	Destabilizing	0.642	D	0.741	deleterious	N	0.397592606	None	None	N
C/S	0.1942	likely_benign	0.1821	benign	-2.256	Highly Destabilizing	0.003	N	0.368	neutral	N	0.35470862	None	None	N
C/T	0.3907	ambiguous	0.3697	ambiguous	-1.879	Destabilizing	0.329	N	0.663	neutral	None	None	None	None	N
C/V	0.4765	ambiguous	0.4606	ambiguous	-1.061	Destabilizing	0.495	N	0.662	neutral	None	None	None	None	N
C/W	0.5721	likely_pathogenic	0.5563	ambiguous	-1.515	Destabilizing	0.993	D	0.707	prob.neutral	N	0.511438186	None	None	N
C/Y	0.3638	ambiguous	0.3522	ambiguous	-1.284	Destabilizing	0.975	D	0.741	deleterious	N	0.452408525	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.