TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29845	89758;89759;89760	chr2:178553367;178553366;178553365	chr2:179418094;179418093;179418092
N2AB	28204	84835;84836;84837	chr2:178553367;178553366;178553365	chr2:179418094;179418093;179418092
N2A	27277	82054;82055;82056	chr2:178553367;178553366;178553365	chr2:179418094;179418093;179418092
N2B	20780	62563;62564;62565	chr2:178553367;178553366;178553365	chr2:179418094;179418093;179418092
Novex-1	20905	62938;62939;62940	chr2:178553367;178553366;178553365	chr2:179418094;179418093;179418092
Novex-2	20972	63139;63140;63141	chr2:178553367;178553366;178553365	chr2:179418094;179418093;179418092
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTC
• RefSeq wild type template codon: GAG
• Domain: Ig-147
• Domain position: 4
• Structural Position: 4
• Q(SASA): 0.2691
• 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
L/V	None	None	0.055	N	0.589	0.192	0.275641507738	gnomAD-4.0.0	1.63021E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.4453E-05	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
L/A	0.6928	likely_pathogenic	0.6601	pathogenic	-1.435	Destabilizing	0.272	N	0.573	neutral	None	None	None	None	N
L/C	0.775	likely_pathogenic	0.7593	pathogenic	-0.949	Destabilizing	0.968	D	0.659	neutral	None	None	None	None	N
L/D	0.9552	likely_pathogenic	0.9509	pathogenic	-0.597	Destabilizing	0.89	D	0.714	prob.delet.	None	None	None	None	N
L/E	0.8208	likely_pathogenic	0.8004	pathogenic	-0.611	Destabilizing	0.726	D	0.701	prob.neutral	None	None	None	None	N
L/F	0.2368	likely_benign	0.1974	benign	-1.076	Destabilizing	0.002	N	0.309	neutral	D	0.534539624	None	None	N
L/G	0.8411	likely_pathogenic	0.8194	pathogenic	-1.74	Destabilizing	0.726	D	0.684	prob.neutral	None	None	None	None	N
L/H	0.6549	likely_pathogenic	0.6138	pathogenic	-1.033	Destabilizing	0.883	D	0.709	prob.delet.	D	0.522105557	None	None	N
L/I	0.2348	likely_benign	0.2232	benign	-0.688	Destabilizing	0.124	N	0.559	neutral	D	0.533576832	None	None	N
L/K	0.7014	likely_pathogenic	0.6704	pathogenic	-0.929	Destabilizing	0.726	D	0.655	neutral	None	None	None	None	N
L/M	0.1569	likely_benign	0.1584	benign	-0.556	Destabilizing	0.014	N	0.334	neutral	None	None	None	None	N
L/N	0.8099	likely_pathogenic	0.7971	pathogenic	-0.68	Destabilizing	0.89	D	0.72	prob.delet.	None	None	None	None	N
L/P	0.8994	likely_pathogenic	0.8524	pathogenic	-0.904	Destabilizing	0.859	D	0.721	prob.delet.	D	0.539449344	None	None	N
L/Q	0.4874	ambiguous	0.4527	ambiguous	-0.836	Destabilizing	0.726	D	0.689	prob.neutral	None	None	None	None	N
L/R	0.6323	likely_pathogenic	0.5923	pathogenic	-0.409	Destabilizing	0.667	D	0.686	prob.neutral	D	0.528346528	None	None	N
L/S	0.7541	likely_pathogenic	0.7269	pathogenic	-1.315	Destabilizing	0.726	D	0.637	neutral	None	None	None	None	N
L/T	0.6704	likely_pathogenic	0.6419	pathogenic	-1.203	Destabilizing	0.726	D	0.625	neutral	None	None	None	None	N
L/V	0.2441	likely_benign	0.227	benign	-0.904	Destabilizing	0.055	N	0.589	neutral	N	0.503464189	None	None	N
L/W	0.4694	ambiguous	0.4034	ambiguous	-1.121	Destabilizing	0.909	D	0.691	prob.neutral	None	None	None	None	N
L/Y	0.6006	likely_pathogenic	0.5575	ambiguous	-0.894	Destabilizing	0.396	N	0.657	neutral	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.