TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5627	17104;17105;17106	chr2:178732090;178732089;178732088	chr2:179596817;179596816;179596815
N2AB	5310	16153;16154;16155	chr2:178732090;178732089;178732088	chr2:179596817;179596816;179596815
N2A	4383	13372;13373;13374	chr2:178732090;178732089;178732088	chr2:179596817;179596816;179596815
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-39
• Domain position: 85
• Structural Position: 169
• Q(SASA): 0.1257
• 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	rs779925659	-1.684	1.0	N	0.921	0.503	0.776795415703	gnomAD-2.1.1	1.21E-05	None	None	None	None	N	None	6.46E-05	0	None	0	0	None	0	None	0	1.79E-05	0
C/R	rs779925659	-1.684	1.0	N	0.921	0.503	0.776795415703	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	4.82E-05	0	0	0	0	None	0	0	0	0	0
C/R	rs779925659	-1.684	1.0	N	0.921	0.503	0.776795415703	gnomAD-4.0.0	3.72368E-06	None	None	None	None	N	None	4.00555E-05	0	None	0	0	None	0	0	2.54646E-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	0.4804	ambiguous	0.4917	ambiguous	-2.442	Highly Destabilizing	0.998	D	0.619	neutral	None	None	None	None	N
C/D	0.863	likely_pathogenic	0.89	pathogenic	-1.473	Destabilizing	1.0	D	0.907	deleterious	None	None	None	None	N
C/E	0.9446	likely_pathogenic	0.9569	pathogenic	-1.323	Destabilizing	1.0	D	0.919	deleterious	None	None	None	None	N
C/F	0.4635	ambiguous	0.4979	ambiguous	-1.533	Destabilizing	1.0	D	0.915	deleterious	N	0.509165863	None	None	N
C/G	0.2563	likely_benign	0.2734	benign	-2.783	Highly Destabilizing	1.0	D	0.861	deleterious	N	0.497644973	None	None	N
C/H	0.7997	likely_pathogenic	0.8219	pathogenic	-2.605	Highly Destabilizing	1.0	D	0.905	deleterious	None	None	None	None	N
C/I	0.638	likely_pathogenic	0.6621	pathogenic	-1.52	Destabilizing	1.0	D	0.836	deleterious	None	None	None	None	N
C/K	0.9633	likely_pathogenic	0.9737	pathogenic	-1.97	Destabilizing	1.0	D	0.904	deleterious	None	None	None	None	N
C/L	0.654	likely_pathogenic	0.6822	pathogenic	-1.52	Destabilizing	0.999	D	0.673	neutral	None	None	None	None	N
C/M	0.7832	likely_pathogenic	0.8166	pathogenic	-0.061	Destabilizing	1.0	D	0.87	deleterious	None	None	None	None	N
C/N	0.7254	likely_pathogenic	0.755	pathogenic	-2.069	Highly Destabilizing	1.0	D	0.919	deleterious	None	None	None	None	N
C/P	0.9923	likely_pathogenic	0.9924	pathogenic	-1.806	Destabilizing	1.0	D	0.918	deleterious	None	None	None	None	N
C/Q	0.8513	likely_pathogenic	0.8818	pathogenic	-1.9	Destabilizing	1.0	D	0.913	deleterious	None	None	None	None	N
C/R	0.7863	likely_pathogenic	0.8201	pathogenic	-1.752	Destabilizing	1.0	D	0.921	deleterious	N	0.495403247	None	None	N
C/S	0.2435	likely_benign	0.2428	benign	-2.618	Highly Destabilizing	1.0	D	0.815	deleterious	N	0.459636434	None	None	N
C/T	0.3863	ambiguous	0.3849	ambiguous	-2.298	Highly Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
C/V	0.5493	ambiguous	0.5583	ambiguous	-1.806	Destabilizing	0.999	D	0.733	prob.delet.	None	None	None	None	N
C/W	0.8404	likely_pathogenic	0.848	pathogenic	-1.579	Destabilizing	1.0	D	0.899	deleterious	N	0.498405442	None	None	N
C/Y	0.6822	likely_pathogenic	0.6967	pathogenic	-1.651	Destabilizing	1.0	D	0.916	deleterious	N	0.503823491	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.