TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9137	27634;27635;27636	chr2:178712513;178712512;178712511	chr2:179577240;179577239;179577238
N2AB	8820	26683;26684;26685	chr2:178712513;178712512;178712511	chr2:179577240;179577239;179577238
N2A	7893	23902;23903;23904	chr2:178712513;178712512;178712511	chr2:179577240;179577239;179577238
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: GGA
• RefSeq wild type template codon: CCT
• Domain: Ig-77
• Domain position: 26
• Structural Position: 40
• Q(SASA): 0.2003
• 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/R	rs1311310606	-0.698	1.0	D	0.819	0.804	0.773199264404	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.87E-06	0
G/R	rs1311310606	-0.698	1.0	D	0.819	0.804	0.773199264404	gnomAD-4.0.0	2.05269E-06	None	None	None	None	N	None	2.98793E-05	0	None	0	0	None	0	0	1.79893E-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	0.5428	ambiguous	0.5992	pathogenic	-0.331	Destabilizing	1.0	D	0.705	prob.neutral	D	0.566483093	None	None	N
G/C	0.9458	likely_pathogenic	0.9501	pathogenic	-0.907	Destabilizing	1.0	D	0.703	prob.neutral	None	None	None	None	N
G/D	0.9759	likely_pathogenic	0.9787	pathogenic	-0.681	Destabilizing	1.0	D	0.842	deleterious	None	None	None	None	N
G/E	0.9858	likely_pathogenic	0.989	pathogenic	-0.829	Destabilizing	1.0	D	0.823	deleterious	D	0.635275269	None	None	N
G/F	0.9953	likely_pathogenic	0.996	pathogenic	-0.972	Destabilizing	1.0	D	0.788	deleterious	None	None	None	None	N
G/H	0.9955	likely_pathogenic	0.9965	pathogenic	-0.651	Destabilizing	1.0	D	0.703	prob.neutral	None	None	None	None	N
G/I	0.9857	likely_pathogenic	0.9884	pathogenic	-0.39	Destabilizing	1.0	D	0.796	deleterious	None	None	None	None	N
G/K	0.9955	likely_pathogenic	0.9969	pathogenic	-0.983	Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	N
G/L	0.9885	likely_pathogenic	0.9907	pathogenic	-0.39	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
G/M	0.9929	likely_pathogenic	0.9946	pathogenic	-0.493	Destabilizing	1.0	D	0.703	prob.neutral	None	None	None	None	N
G/N	0.9833	likely_pathogenic	0.9852	pathogenic	-0.621	Destabilizing	1.0	D	0.816	deleterious	None	None	None	None	N
G/P	0.9972	likely_pathogenic	0.9979	pathogenic	-0.336	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
G/Q	0.9902	likely_pathogenic	0.9924	pathogenic	-0.882	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
G/R	0.9838	likely_pathogenic	0.9881	pathogenic	-0.545	Destabilizing	1.0	D	0.819	deleterious	D	0.654927107	None	None	N
G/S	0.6595	likely_pathogenic	0.6992	pathogenic	-0.757	Destabilizing	1.0	D	0.788	deleterious	None	None	None	None	N
G/T	0.9486	likely_pathogenic	0.9609	pathogenic	-0.832	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
G/V	0.963	likely_pathogenic	0.9684	pathogenic	-0.336	Destabilizing	1.0	D	0.815	deleterious	D	0.629388995	None	None	N
G/W	0.993	likely_pathogenic	0.9941	pathogenic	-1.167	Destabilizing	1.0	D	0.694	prob.neutral	None	None	None	None	N
G/Y	0.9934	likely_pathogenic	0.9946	pathogenic	-0.81	Destabilizing	1.0	D	0.778	deleterious	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.