TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20508	61747;61748;61749	chr2:178590203;178590202;178590201	chr2:179454930;179454929;179454928
N2AB	18867	56824;56825;56826	chr2:178590203;178590202;178590201	chr2:179454930;179454929;179454928
N2A	17940	54043;54044;54045	chr2:178590203;178590202;178590201	chr2:179454930;179454929;179454928
N2B	11443	34552;34553;34554	chr2:178590203;178590202;178590201	chr2:179454930;179454929;179454928
Novex-1	11568	34927;34928;34929	chr2:178590203;178590202;178590201	chr2:179454930;179454929;179454928
Novex-2	11635	35128;35129;35130	chr2:178590203;178590202;178590201	chr2:179454930;179454929;179454928
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATA
• RefSeq wild type template codon: TAT
• Domain: Ig-121
• Domain position: 30
• Structural Position: 46
• Q(SASA): 0.2202
• Predicted PPI site: I

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
I/V	None	None	0.046	N	0.211	0.088	0.382925413656	gnomAD-4.0.0	4.80129E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	5.25001E-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
I/A	0.704	likely_pathogenic	0.7623	pathogenic	-2.17	Highly Destabilizing	0.825	D	0.739	prob.delet.	None	None	None	None	I
I/C	0.7166	likely_pathogenic	0.742	pathogenic	-1.428	Destabilizing	0.999	D	0.719	prob.delet.	None	None	None	None	I
I/D	0.9741	likely_pathogenic	0.9836	pathogenic	-1.682	Destabilizing	0.996	D	0.855	deleterious	None	None	None	None	I
I/E	0.9409	likely_pathogenic	0.9585	pathogenic	-1.597	Destabilizing	0.988	D	0.853	deleterious	None	None	None	None	I
I/F	0.2677	likely_benign	0.2924	benign	-1.466	Destabilizing	0.976	D	0.7	prob.neutral	None	None	None	None	I
I/G	0.9318	likely_pathogenic	0.9547	pathogenic	-2.583	Highly Destabilizing	0.988	D	0.84	deleterious	None	None	None	None	I
I/H	0.8721	likely_pathogenic	0.9065	pathogenic	-1.737	Destabilizing	0.999	D	0.829	deleterious	None	None	None	None	I
I/K	0.8193	likely_pathogenic	0.859	pathogenic	-1.571	Destabilizing	0.984	D	0.851	deleterious	D	0.53148467	None	None	I
I/L	0.178	likely_benign	0.1898	benign	-1.052	Destabilizing	0.211	N	0.458	neutral	D	0.526099073	None	None	I
I/M	0.1563	likely_benign	0.1615	benign	-0.872	Destabilizing	0.64	D	0.51	neutral	D	0.53097769	None	None	I
I/N	0.7563	likely_pathogenic	0.8186	pathogenic	-1.493	Destabilizing	0.996	D	0.85	deleterious	None	None	None	None	I
I/P	0.9574	likely_pathogenic	0.9694	pathogenic	-1.398	Destabilizing	0.996	D	0.852	deleterious	None	None	None	None	I
I/Q	0.8618	likely_pathogenic	0.8941	pathogenic	-1.559	Destabilizing	0.988	D	0.849	deleterious	None	None	None	None	I
I/R	0.7668	likely_pathogenic	0.8241	pathogenic	-1.05	Destabilizing	0.984	D	0.851	deleterious	D	0.542840975	None	None	I
I/S	0.7269	likely_pathogenic	0.7983	pathogenic	-2.173	Highly Destabilizing	0.988	D	0.839	deleterious	None	None	None	None	I
I/T	0.5387	ambiguous	0.604	pathogenic	-1.946	Destabilizing	0.896	D	0.771	deleterious	N	0.510240089	None	None	I
I/V	0.0889	likely_benign	0.0839	benign	-1.398	Destabilizing	0.046	N	0.211	neutral	N	0.42563293	None	None	I
I/W	0.9149	likely_pathogenic	0.9237	pathogenic	-1.569	Destabilizing	0.999	D	0.846	deleterious	None	None	None	None	I
I/Y	0.7096	likely_pathogenic	0.7458	pathogenic	-1.365	Destabilizing	0.988	D	0.737	prob.delet.	None	None	None	None	I

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.