TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6174	18745;18746;18747	chr2:178729733;178729732;178729731	chr2:179594460;179594459;179594458
N2AB	5857	17794;17795;17796	chr2:178729733;178729732;178729731	chr2:179594460;179594459;179594458
N2A	4930	15013;15014;15015	chr2:178729733;178729732;178729731	chr2:179594460;179594459;179594458
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: G
• RefSeq wild type transcript codon: GGG
• RefSeq wild type template codon: CCC
• Domain: Ig-45
• Domain position: 70
• Structural Position: 152
• Q(SASA): 0.1951
• 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
G/V	None	None	1.0	D	0.747	0.623	0.96544231252	gnomAD-4.0.0	4.78963E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	6.2965E-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
G/A	0.3221	likely_benign	0.3606	ambiguous	-0.785	Destabilizing	1.0	D	0.747	deleterious	D	0.596537672	None	None	N
G/C	0.6988	likely_pathogenic	0.752	pathogenic	-1.108	Destabilizing	1.0	D	0.713	prob.delet.	None	None	None	None	N
G/D	0.7173	likely_pathogenic	0.7775	pathogenic	-1.124	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
G/E	0.7644	likely_pathogenic	0.815	pathogenic	-1.114	Destabilizing	1.0	D	0.787	deleterious	D	0.682931488	None	None	N
G/F	0.9448	likely_pathogenic	0.9545	pathogenic	-0.999	Destabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	N
G/H	0.8389	likely_pathogenic	0.8801	pathogenic	-1.483	Destabilizing	1.0	D	0.687	prob.neutral	None	None	None	None	N
G/I	0.9196	likely_pathogenic	0.9358	pathogenic	-0.169	Destabilizing	1.0	D	0.742	deleterious	None	None	None	None	N
G/K	0.7502	likely_pathogenic	0.8048	pathogenic	-1.151	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
G/L	0.8999	likely_pathogenic	0.9198	pathogenic	-0.169	Destabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	N
G/M	0.9227	likely_pathogenic	0.9394	pathogenic	-0.25	Destabilizing	1.0	D	0.711	prob.delet.	None	None	None	None	N
G/N	0.7812	likely_pathogenic	0.8255	pathogenic	-0.985	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
G/P	0.9903	likely_pathogenic	0.9922	pathogenic	-0.331	Destabilizing	1.0	D	0.771	deleterious	None	None	None	None	N
G/Q	0.7127	likely_pathogenic	0.7747	pathogenic	-1.054	Destabilizing	1.0	D	0.774	deleterious	None	None	None	None	N
G/R	0.5666	likely_pathogenic	0.6366	pathogenic	-1.007	Destabilizing	1.0	D	0.783	deleterious	D	0.682931488	None	None	N
G/S	0.29	likely_benign	0.3376	benign	-1.37	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
G/T	0.731	likely_pathogenic	0.7773	pathogenic	-1.254	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
G/V	0.8396	likely_pathogenic	0.868	pathogenic	-0.331	Destabilizing	1.0	D	0.747	deleterious	D	0.682931488	None	None	N
G/W	0.9026	likely_pathogenic	0.9267	pathogenic	-1.441	Destabilizing	1.0	D	0.729	prob.delet.	D	0.683133292	None	None	N
G/Y	0.91	likely_pathogenic	0.934	pathogenic	-0.961	Destabilizing	1.0	D	0.721	prob.delet.	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.