TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8998	27217;27218;27219	chr2:178713142;178713141;178713140	chr2:179577869;179577868;179577867
N2AB	8681	26266;26267;26268	chr2:178713142;178713141;178713140	chr2:179577869;179577868;179577867
N2A	7754	23485;23486;23487	chr2:178713142;178713141;178713140	chr2:179577869;179577868;179577867
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-75
• Domain position: 73
• Structural Position: 156
• Q(SASA): 0.0627
• 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/G	rs992449953	None	1.0	D	0.875	0.725	0.836894289642	gnomAD-4.0.0	1.20032E-06	None	None	disulfide	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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	0.8993	likely_pathogenic	0.9148	pathogenic	-1.471	Destabilizing	0.998	D	0.725	prob.delet.	None	None	disulfide	None	N
C/D	0.9997	likely_pathogenic	0.9998	pathogenic	-1.498	Destabilizing	1.0	D	0.881	deleterious	None	None	disulfide	None	N
C/E	0.9998	likely_pathogenic	0.9998	pathogenic	-1.251	Destabilizing	1.0	D	0.9	deleterious	None	None	disulfide	None	N
C/F	0.879	likely_pathogenic	0.9138	pathogenic	-0.873	Destabilizing	1.0	D	0.891	deleterious	D	0.538987909	disulfide	None	N
C/G	0.8829	likely_pathogenic	0.9147	pathogenic	-1.811	Destabilizing	1.0	D	0.875	deleterious	D	0.563386041	disulfide	None	N
C/H	0.9986	likely_pathogenic	0.999	pathogenic	-2.036	Highly Destabilizing	1.0	D	0.897	deleterious	None	None	disulfide	None	N
C/I	0.8946	likely_pathogenic	0.9141	pathogenic	-0.54	Destabilizing	1.0	D	0.816	deleterious	None	None	disulfide	None	N
C/K	0.9998	likely_pathogenic	0.9998	pathogenic	-0.92	Destabilizing	1.0	D	0.879	deleterious	None	None	disulfide	None	N
C/L	0.8506	likely_pathogenic	0.8759	pathogenic	-0.54	Destabilizing	0.999	D	0.773	deleterious	None	None	disulfide	None	N
C/M	0.9594	likely_pathogenic	0.9677	pathogenic	-0.115	Destabilizing	1.0	D	0.835	deleterious	None	None	disulfide	None	N
C/N	0.9982	likely_pathogenic	0.9987	pathogenic	-1.547	Destabilizing	1.0	D	0.9	deleterious	None	None	disulfide	None	N
C/P	0.9993	likely_pathogenic	0.9995	pathogenic	-0.83	Destabilizing	1.0	D	0.899	deleterious	None	None	disulfide	None	N
C/Q	0.9991	likely_pathogenic	0.9994	pathogenic	-1.024	Destabilizing	1.0	D	0.908	deleterious	None	None	disulfide	None	N
C/R	0.9964	likely_pathogenic	0.9974	pathogenic	-1.462	Destabilizing	1.0	D	0.903	deleterious	D	0.563386041	disulfide	None	N
C/S	0.9672	likely_pathogenic	0.9758	pathogenic	-1.799	Destabilizing	1.0	D	0.805	deleterious	D	0.563386041	disulfide	None	N
C/T	0.9819	likely_pathogenic	0.9865	pathogenic	-1.381	Destabilizing	1.0	D	0.817	deleterious	None	None	disulfide	None	N
C/V	0.7788	likely_pathogenic	0.7978	pathogenic	-0.83	Destabilizing	0.999	D	0.795	deleterious	None	None	disulfide	None	N
C/W	0.9937	likely_pathogenic	0.996	pathogenic	-1.339	Destabilizing	1.0	D	0.869	deleterious	D	0.563386041	disulfide	None	N
C/Y	0.9846	likely_pathogenic	0.9905	pathogenic	-1.094	Destabilizing	1.0	D	0.902	deleterious	D	0.563386041	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.