TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28192	84799;84800;84801	chr2:178561558;178561557;178561556	chr2:179426285;179426284;179426283
N2AB	26551	79876;79877;79878	chr2:178561558;178561557;178561556	chr2:179426285;179426284;179426283
N2A	25624	77095;77096;77097	chr2:178561558;178561557;178561556	chr2:179426285;179426284;179426283
N2B	19127	57604;57605;57606	chr2:178561558;178561557;178561556	chr2:179426285;179426284;179426283
Novex-1	19252	57979;57980;57981	chr2:178561558;178561557;178561556	chr2:179426285;179426284;179426283
Novex-2	19319	58180;58181;58182	chr2:178561558;178561557;178561556	chr2:179426285;179426284;179426283
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: Fn3-93
• Domain position: 39
• Structural Position: 41
• Q(SASA): 0.1185
• 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/K	rs879123930	None	0.999	N	0.681	0.444	0.37568098594	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
E/K	rs879123930	None	0.999	N	0.681	0.444	0.37568098594	gnomAD-4.0.0	2.47956E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.39105E-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	0.8214	likely_pathogenic	0.8081	pathogenic	-0.746	Destabilizing	0.999	D	0.691	prob.neutral	D	0.542433133	None	None	N
E/C	0.9841	likely_pathogenic	0.9803	pathogenic	-0.084	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	N
E/D	0.813	likely_pathogenic	0.8051	pathogenic	-1.638	Destabilizing	0.999	D	0.653	neutral	N	0.480802987	None	None	N
E/F	0.9886	likely_pathogenic	0.9862	pathogenic	-0.455	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
E/G	0.919	likely_pathogenic	0.9091	pathogenic	-1.15	Destabilizing	1.0	D	0.757	deleterious	D	0.544207559	None	None	N
E/H	0.9677	likely_pathogenic	0.9624	pathogenic	-0.372	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
E/I	0.9632	likely_pathogenic	0.9574	pathogenic	0.402	Stabilizing	1.0	D	0.814	deleterious	None	None	None	None	N
E/K	0.9639	likely_pathogenic	0.9594	pathogenic	-0.796	Destabilizing	0.999	D	0.681	prob.neutral	N	0.505121759	None	None	N
E/L	0.9608	likely_pathogenic	0.9567	pathogenic	0.402	Stabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
E/M	0.9574	likely_pathogenic	0.9495	pathogenic	1.0	Stabilizing	1.0	D	0.774	deleterious	None	None	None	None	N
E/N	0.9733	likely_pathogenic	0.9676	pathogenic	-1.172	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
E/P	0.9995	likely_pathogenic	0.9991	pathogenic	0.036	Stabilizing	1.0	D	0.782	deleterious	None	None	None	None	N
E/Q	0.6558	likely_pathogenic	0.6306	pathogenic	-0.842	Destabilizing	1.0	D	0.75	deleterious	N	0.480420912	None	None	N
E/R	0.9617	likely_pathogenic	0.9587	pathogenic	-0.789	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
E/S	0.9004	likely_pathogenic	0.8957	pathogenic	-1.683	Destabilizing	0.999	D	0.739	prob.delet.	None	None	None	None	N
E/T	0.9569	likely_pathogenic	0.9533	pathogenic	-1.293	Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	N
E/V	0.9129	likely_pathogenic	0.9028	pathogenic	0.036	Stabilizing	1.0	D	0.757	deleterious	N	0.52048099	None	None	N
E/W	0.9962	likely_pathogenic	0.9952	pathogenic	-0.644	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	N
E/Y	0.9823	likely_pathogenic	0.9772	pathogenic	-0.255	Destabilizing	1.0	D	0.783	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.