TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6364	19315;19316;19317	chr2:178728948;178728947;178728946	chr2:179593675;179593674;179593673
N2AB	6047	18364;18365;18366	chr2:178728948;178728947;178728946	chr2:179593675;179593674;179593673
N2A	5120	15583;15584;15585	chr2:178728948;178728947;178728946	chr2:179593675;179593674;179593673
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: C
• RefSeq wild type transcript codon: TGT
• RefSeq wild type template codon: ACA
• Domain: Ig-47
• Domain position: 73
• Structural Position: 156
• Q(SASA): 0.0617
• 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	None	None	1.0	D	0.9	0.649	0.85943983745	gnomAD-4.0.0	6.85015E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.00113E-07	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
C/A	0.8653	likely_pathogenic	0.8436	pathogenic	-1.39	Destabilizing	0.998	D	0.721	prob.delet.	None	None	None	None	N
C/D	0.9996	likely_pathogenic	0.9995	pathogenic	-1.508	Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	N
C/E	0.9996	likely_pathogenic	0.9996	pathogenic	-1.256	Destabilizing	1.0	D	0.901	deleterious	None	None	None	None	N
C/F	0.676	likely_pathogenic	0.7322	pathogenic	-0.83	Destabilizing	1.0	D	0.89	deleterious	D	0.56927139	None	None	N
C/G	0.8275	likely_pathogenic	0.808	pathogenic	-1.718	Destabilizing	1.0	D	0.875	deleterious	D	0.570792327	None	None	N
C/H	0.9961	likely_pathogenic	0.9961	pathogenic	-1.842	Destabilizing	1.0	D	0.895	deleterious	None	None	None	None	N
C/I	0.7727	likely_pathogenic	0.7528	pathogenic	-0.49	Destabilizing	1.0	D	0.81	deleterious	None	None	None	None	N
C/K	0.9997	likely_pathogenic	0.9996	pathogenic	-0.803	Destabilizing	1.0	D	0.88	deleterious	None	None	None	None	N
C/L	0.6986	likely_pathogenic	0.6763	pathogenic	-0.49	Destabilizing	0.999	D	0.769	deleterious	None	None	None	None	N
C/M	0.9124	likely_pathogenic	0.9065	pathogenic	-0.459	Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	N
C/N	0.9958	likely_pathogenic	0.9949	pathogenic	-1.47	Destabilizing	1.0	D	0.901	deleterious	None	None	None	None	N
C/P	0.9992	likely_pathogenic	0.9991	pathogenic	-0.772	Destabilizing	1.0	D	0.901	deleterious	None	None	None	None	N
C/Q	0.9979	likely_pathogenic	0.9976	pathogenic	-0.953	Destabilizing	1.0	D	0.907	deleterious	None	None	None	None	N
C/R	0.9948	likely_pathogenic	0.9945	pathogenic	-1.353	Destabilizing	1.0	D	0.904	deleterious	D	0.570792327	None	None	N
C/S	0.936	likely_pathogenic	0.9266	pathogenic	-1.686	Destabilizing	1.0	D	0.8	deleterious	D	0.570792327	None	None	N
C/T	0.9565	likely_pathogenic	0.9489	pathogenic	-1.269	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
C/V	0.6503	likely_pathogenic	0.6165	pathogenic	-0.772	Destabilizing	0.999	D	0.792	deleterious	None	None	None	None	N
C/W	0.9821	likely_pathogenic	0.9863	pathogenic	-1.257	Destabilizing	1.0	D	0.865	deleterious	D	0.570792327	None	None	N
C/Y	0.9506	likely_pathogenic	0.959	pathogenic	-1.009	Destabilizing	1.0	D	0.9	deleterious	D	0.570792327	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.