TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6965	21118;21119;21120	chr2:178724482;178724481;178724480	chr2:179589209;179589208;179589207
N2AB	6648	20167;20168;20169	chr2:178724482;178724481;178724480	chr2:179589209;179589208;179589207
N2A	5721	17386;17387;17388	chr2:178724482;178724481;178724480	chr2:179589209;179589208;179589207
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: TGC
• RefSeq wild type template codon: ACG
• Domain: Ig-54
• Domain position: 18
• Structural Position: 28
• Q(SASA): 0.1426
• 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/R	None	None	0.988	N	0.737	0.32	0.705616693011	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.66327E-05
C/Y	None	None	0.996	N	0.719	0.282	0.571967413633	gnomAD-4.0.0	1.59492E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86633E-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
C/A	0.4121	ambiguous	0.3641	ambiguous	-2.056	Highly Destabilizing	0.028	N	0.163	neutral	None	None	None	None	N
C/D	0.972	likely_pathogenic	0.9694	pathogenic	-0.889	Destabilizing	0.969	D	0.721	prob.delet.	None	None	None	None	N
C/E	0.9805	likely_pathogenic	0.9797	pathogenic	-0.732	Destabilizing	0.969	D	0.703	prob.neutral	None	None	None	None	N
C/F	0.2816	likely_benign	0.2565	benign	-1.235	Destabilizing	0.996	D	0.722	prob.delet.	N	0.405990297	None	None	N
C/G	0.2909	likely_benign	0.2744	benign	-2.415	Highly Destabilizing	0.704	D	0.629	neutral	N	0.403624783	None	None	N
C/H	0.9004	likely_pathogenic	0.8917	pathogenic	-2.286	Highly Destabilizing	0.999	D	0.709	prob.delet.	None	None	None	None	N
C/I	0.5326	ambiguous	0.447	ambiguous	-1.103	Destabilizing	0.969	D	0.671	neutral	None	None	None	None	N
C/K	0.9779	likely_pathogenic	0.9791	pathogenic	-1.419	Destabilizing	0.939	D	0.699	prob.neutral	None	None	None	None	N
C/L	0.4621	ambiguous	0.413	ambiguous	-1.103	Destabilizing	0.863	D	0.582	neutral	None	None	None	None	N
C/M	0.701	likely_pathogenic	0.6691	pathogenic	0.096	Stabilizing	0.997	D	0.705	prob.neutral	None	None	None	None	N
C/N	0.9094	likely_pathogenic	0.8947	pathogenic	-1.617	Destabilizing	0.997	D	0.741	deleterious	None	None	None	None	N
C/P	0.9846	likely_pathogenic	0.9845	pathogenic	-1.396	Destabilizing	0.046	N	0.494	neutral	None	None	None	None	N
C/Q	0.9289	likely_pathogenic	0.9271	pathogenic	-1.394	Destabilizing	0.997	D	0.737	prob.delet.	None	None	None	None	N
C/R	0.8546	likely_pathogenic	0.8606	pathogenic	-1.323	Destabilizing	0.988	D	0.737	prob.delet.	N	0.462614371	None	None	N
C/S	0.5061	ambiguous	0.4366	ambiguous	-2.169	Highly Destabilizing	0.704	D	0.582	neutral	N	0.462441013	None	None	N
C/T	0.6335	likely_pathogenic	0.5855	pathogenic	-1.812	Destabilizing	0.939	D	0.631	neutral	None	None	None	None	N
C/V	0.4157	ambiguous	0.3471	ambiguous	-1.396	Destabilizing	0.863	D	0.592	neutral	None	None	None	None	N
C/W	0.8006	likely_pathogenic	0.7692	pathogenic	-1.265	Destabilizing	0.999	D	0.669	neutral	N	0.481816207	None	None	N
C/Y	0.5796	likely_pathogenic	0.5333	ambiguous	-1.285	Destabilizing	0.996	D	0.719	prob.delet.	N	0.44402861	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.