TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21919	65980;65981;65982	chr2:178583048;178583047;178583046	chr2:179447775;179447774;179447773
N2AB	20278	61057;61058;61059	chr2:178583048;178583047;178583046	chr2:179447775;179447774;179447773
N2A	19351	58276;58277;58278	chr2:178583048;178583047;178583046	chr2:179447775;179447774;179447773
N2B	12854	38785;38786;38787	chr2:178583048;178583047;178583046	chr2:179447775;179447774;179447773
Novex-1	12979	39160;39161;39162	chr2:178583048;178583047;178583046	chr2:179447775;179447774;179447773
Novex-2	13046	39361;39362;39363	chr2:178583048;178583047;178583046	chr2:179447775;179447774;179447773
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-125
• Domain position: 54
• Structural Position: 136
• Q(SASA): 0.0948
• 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/Y	rs1403325884	-1.82	0.512	N	0.699	0.182	0.428401797576	gnomAD-2.1.1	4.07E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	9.01E-06	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	0.4754	ambiguous	0.457	ambiguous	-2.065	Highly Destabilizing	0.001	N	0.273	neutral	None	None	None	None	N
C/D	0.9644	likely_pathogenic	0.9431	pathogenic	-1.457	Destabilizing	0.223	N	0.72	prob.delet.	None	None	None	None	N
C/E	0.9733	likely_pathogenic	0.958	pathogenic	-1.271	Destabilizing	0.365	N	0.74	deleterious	None	None	None	None	N
C/F	0.3023	likely_benign	0.2268	benign	-1.443	Destabilizing	0.512	D	0.707	prob.neutral	N	0.408779886	None	None	N
C/G	0.4328	ambiguous	0.3947	ambiguous	-2.425	Highly Destabilizing	0.086	N	0.716	prob.delet.	N	0.372744515	None	None	N
C/H	0.6956	likely_pathogenic	0.5804	pathogenic	-2.618	Highly Destabilizing	0.001	N	0.583	neutral	None	None	None	None	N
C/I	0.6916	likely_pathogenic	0.619	pathogenic	-1.098	Destabilizing	0.223	N	0.699	prob.neutral	None	None	None	None	N
C/K	0.9658	likely_pathogenic	0.9431	pathogenic	-1.417	Destabilizing	0.365	N	0.733	prob.delet.	None	None	None	None	N
C/L	0.564	likely_pathogenic	0.516	ambiguous	-1.098	Destabilizing	0.001	N	0.459	neutral	None	None	None	None	N
C/M	0.7302	likely_pathogenic	0.685	pathogenic	0.209	Stabilizing	0.83	D	0.722	prob.delet.	None	None	None	None	N
C/N	0.8123	likely_pathogenic	0.7415	pathogenic	-1.797	Destabilizing	0.008	N	0.603	neutral	None	None	None	None	N
C/P	0.9881	likely_pathogenic	0.9834	pathogenic	-1.397	Destabilizing	0.738	D	0.717	prob.delet.	None	None	None	None	N
C/Q	0.8788	likely_pathogenic	0.8245	pathogenic	-1.494	Destabilizing	0.738	D	0.722	prob.delet.	None	None	None	None	N
C/R	0.8594	likely_pathogenic	0.7815	pathogenic	-1.583	Destabilizing	0.302	N	0.688	prob.neutral	N	0.422402545	None	None	N
C/S	0.4159	ambiguous	0.3683	ambiguous	-2.203	Highly Destabilizing	0.086	N	0.655	neutral	N	0.384036157	None	None	N
C/T	0.5673	likely_pathogenic	0.5084	ambiguous	-1.822	Destabilizing	0.003	N	0.422	neutral	None	None	None	None	N
C/V	0.5239	ambiguous	0.4743	ambiguous	-1.397	Destabilizing	0.111	N	0.643	neutral	None	None	None	None	N
C/W	0.7125	likely_pathogenic	0.6059	pathogenic	-1.646	Destabilizing	0.988	D	0.694	prob.neutral	N	0.43440905	None	None	N
C/Y	0.4322	ambiguous	0.3223	benign	-1.566	Destabilizing	0.512	D	0.699	prob.neutral	N	0.419900957	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.