TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25044	75355;75356;75357	chr2:178571002;178571001;178571000	chr2:179435729;179435728;179435727
N2AB	23403	70432;70433;70434	chr2:178571002;178571001;178571000	chr2:179435729;179435728;179435727
N2A	22476	67651;67652;67653	chr2:178571002;178571001;178571000	chr2:179435729;179435728;179435727
N2B	15979	48160;48161;48162	chr2:178571002;178571001;178571000	chr2:179435729;179435728;179435727
Novex-1	16104	48535;48536;48537	chr2:178571002;178571001;178571000	chr2:179435729;179435728;179435727
Novex-2	16171	48736;48737;48738	chr2:178571002;178571001;178571000	chr2:179435729;179435728;179435727
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: Fn3-70
• Domain position: 39
• Structural Position: 41
• Q(SASA): 0.1368
• 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	None	None	0.999	N	0.633	0.308	0.350746614512	gnomAD-4.0.0	1.36879E-06	None	None	None	None	N	None	5.98229E-05	0	None	0	0	None	0	0	0	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	0.9422	likely_pathogenic	0.9397	pathogenic	-1.641	Destabilizing	0.999	D	0.685	prob.neutral	D	0.539635202	None	None	N
E/C	0.9909	likely_pathogenic	0.9891	pathogenic	-0.873	Destabilizing	1.0	D	0.782	deleterious	None	None	None	None	N
E/D	0.9651	likely_pathogenic	0.9663	pathogenic	-1.783	Destabilizing	0.999	D	0.633	neutral	N	0.489032194	None	None	N
E/F	0.9958	likely_pathogenic	0.9951	pathogenic	-1.287	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
E/G	0.965	likely_pathogenic	0.9609	pathogenic	-2.032	Highly Destabilizing	1.0	D	0.761	deleterious	D	0.534661679	None	None	N
E/H	0.9889	likely_pathogenic	0.9875	pathogenic	-1.21	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	N
E/I	0.9834	likely_pathogenic	0.9816	pathogenic	-0.512	Destabilizing	1.0	D	0.818	deleterious	None	None	None	None	N
E/K	0.9649	likely_pathogenic	0.9601	pathogenic	-1.713	Destabilizing	0.999	D	0.664	neutral	N	0.5202635	None	None	N
E/L	0.9791	likely_pathogenic	0.9764	pathogenic	-0.512	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
E/M	0.9747	likely_pathogenic	0.9721	pathogenic	0.231	Stabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
E/N	0.9921	likely_pathogenic	0.9913	pathogenic	-1.923	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
E/P	0.9998	likely_pathogenic	0.9998	pathogenic	-0.875	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
E/Q	0.7726	likely_pathogenic	0.7546	pathogenic	-1.617	Destabilizing	1.0	D	0.743	deleterious	N	0.471533369	None	None	N
E/R	0.9746	likely_pathogenic	0.9718	pathogenic	-1.522	Destabilizing	1.0	D	0.792	deleterious	None	None	None	None	N
E/S	0.9591	likely_pathogenic	0.957	pathogenic	-2.56	Highly Destabilizing	0.999	D	0.727	prob.delet.	None	None	None	None	N
E/T	0.9796	likely_pathogenic	0.978	pathogenic	-2.19	Highly Destabilizing	1.0	D	0.778	deleterious	None	None	None	None	N
E/V	0.9605	likely_pathogenic	0.9579	pathogenic	-0.875	Destabilizing	1.0	D	0.763	deleterious	D	0.533647721	None	None	N
E/W	0.9976	likely_pathogenic	0.9974	pathogenic	-1.374	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
E/Y	0.9922	likely_pathogenic	0.9914	pathogenic	-1.124	Destabilizing	1.0	D	0.789	deleterious	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.