TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9277	28054;28055;28056	chr2:178712001;178712000;178711999	chr2:179576728;179576727;179576726
N2AB	8960	27103;27104;27105	chr2:178712001;178712000;178711999	chr2:179576728;179576727;179576726
N2A	8033	24322;24323;24324	chr2:178712001;178712000;178711999	chr2:179576728;179576727;179576726
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-78
• Domain position: 73
• Structural Position: 156
• Q(SASA): 0.0654
• Site annotation: disulfide
• 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/S	None	None	1.0	D	0.8	0.733	0.787498767372	gnomAD-4.0.0	7.20193E-06	None	None	disulfide	None	N	None	0	0	None	0	0	None	0	0	7.87501E-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	0.951	likely_pathogenic	0.96	pathogenic	-1.443	Destabilizing	0.998	D	0.732	prob.delet.	None	None	disulfide	None	N
C/D	0.9998	likely_pathogenic	0.9999	pathogenic	-1.189	Destabilizing	1.0	D	0.879	deleterious	None	None	disulfide	None	N
C/E	0.9997	likely_pathogenic	0.9999	pathogenic	-0.928	Destabilizing	1.0	D	0.895	deleterious	None	None	disulfide	None	N
C/F	0.8396	likely_pathogenic	0.9193	pathogenic	-0.823	Destabilizing	1.0	D	0.888	deleterious	D	0.55412965	disulfide	None	N
C/G	0.9114	likely_pathogenic	0.9479	pathogenic	-1.825	Destabilizing	1.0	D	0.866	deleterious	D	0.567006892	disulfide	None	N
C/H	0.9982	likely_pathogenic	0.9994	pathogenic	-1.984	Destabilizing	1.0	D	0.895	deleterious	None	None	disulfide	None	N
C/I	0.8351	likely_pathogenic	0.8295	pathogenic	-0.401	Destabilizing	1.0	D	0.807	deleterious	None	None	disulfide	None	N
C/K	0.9997	likely_pathogenic	0.9999	pathogenic	-0.617	Destabilizing	1.0	D	0.877	deleterious	None	None	disulfide	None	N
C/L	0.7418	likely_pathogenic	0.808	pathogenic	-0.401	Destabilizing	0.999	D	0.776	deleterious	None	None	disulfide	None	N
C/M	0.9551	likely_pathogenic	0.9667	pathogenic	0.313	Stabilizing	1.0	D	0.833	deleterious	None	None	disulfide	None	N
C/N	0.9984	likely_pathogenic	0.9992	pathogenic	-1.351	Destabilizing	1.0	D	0.895	deleterious	None	None	disulfide	None	N
C/P	0.999	likely_pathogenic	0.9994	pathogenic	-0.726	Destabilizing	1.0	D	0.894	deleterious	None	None	disulfide	None	N
C/Q	0.9986	likely_pathogenic	0.9995	pathogenic	-0.811	Destabilizing	1.0	D	0.907	deleterious	None	None	disulfide	None	N
C/R	0.9952	likely_pathogenic	0.9981	pathogenic	-1.199	Destabilizing	1.0	D	0.9	deleterious	D	0.567006892	disulfide	None	N
C/S	0.9795	likely_pathogenic	0.9862	pathogenic	-1.632	Destabilizing	1.0	D	0.8	deleterious	D	0.567006892	disulfide	None	N
C/T	0.9836	likely_pathogenic	0.9877	pathogenic	-1.169	Destabilizing	1.0	D	0.811	deleterious	None	None	disulfide	None	N
C/V	0.7796	likely_pathogenic	0.753	pathogenic	-0.726	Destabilizing	0.999	D	0.79	deleterious	None	None	disulfide	None	N
C/W	0.9882	likely_pathogenic	0.9953	pathogenic	-1.195	Destabilizing	1.0	D	0.87	deleterious	D	0.567006892	disulfide	None	N
C/Y	0.9809	likely_pathogenic	0.992	pathogenic	-0.971	Destabilizing	1.0	D	0.899	deleterious	D	0.567006892	disulfide	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.