TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3955	12088;12089;12090	chr2:178741370;178741369;178741368	chr2:179606097;179606096;179606095
N2AB	3638	11137;11138;11139	chr2:178741370;178741369;178741368	chr2:179606097;179606096;179606095
N2A	None	None	chr2:None	chr2:None
N2B	3592	10999;11000;11001	chr2:178741370;178741369;178741368	chr2:179606097;179606096;179606095
Novex-1	3717	11374;11375;11376	chr2:178741370;178741369;178741368	chr2:179606097;179606096;179606095
Novex-2	3784	11575;11576;11577	chr2:178741370;178741369;178741368	chr2:179606097;179606096;179606095
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCC
• RefSeq wild type template codon: CGG
• Domain: Ig-28
• Domain position: 18
• Structural Position: 28
• Q(SASA): 0.173
• 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
A/P	None	None	0.999	D	0.783	0.428	None	gnomAD-4.0.0	1.59107E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	0	3.02389E-05
A/S	rs1352554984	-1.391	0.989	D	0.58	0.352	None	gnomAD-2.1.1	7.14E-06	None	None	None	None	I	None	0	2.83E-05	None	0	0	None	0	None	0	0	1.40292E-04
A/S	rs1352554984	-1.391	0.989	D	0.58	0.352	None	gnomAD-4.0.0	3.18215E-06	None	None	None	None	I	None	0	4.57247E-05	None	0	0	None	0	0	0	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
A/C	0.7198	likely_pathogenic	0.7132	pathogenic	-0.608	Destabilizing	1.0	D	0.677	prob.neutral	None	None	None	None	I
A/D	0.9638	likely_pathogenic	0.973	pathogenic	-1.968	Destabilizing	0.999	D	0.77	deleterious	D	0.68778658	None	None	I
A/E	0.9332	likely_pathogenic	0.952	pathogenic	-1.763	Destabilizing	0.999	D	0.771	deleterious	None	None	None	None	I
A/F	0.888	likely_pathogenic	0.9105	pathogenic	-0.539	Destabilizing	0.998	D	0.743	deleterious	None	None	None	None	I
A/G	0.3611	ambiguous	0.3492	ambiguous	-1.26	Destabilizing	0.996	D	0.559	neutral	D	0.587381813	None	None	I
A/H	0.9723	likely_pathogenic	0.9793	pathogenic	-1.812	Destabilizing	1.0	D	0.74	deleterious	None	None	None	None	I
A/I	0.6209	likely_pathogenic	0.648	pathogenic	0.49	Stabilizing	0.967	D	0.601	neutral	None	None	None	None	I
A/K	0.9756	likely_pathogenic	0.9832	pathogenic	-1.089	Destabilizing	0.998	D	0.769	deleterious	None	None	None	None	I
A/L	0.6447	likely_pathogenic	0.6826	pathogenic	0.49	Stabilizing	0.923	D	0.588	neutral	None	None	None	None	I
A/M	0.6926	likely_pathogenic	0.7421	pathogenic	0.375	Stabilizing	0.998	D	0.745	deleterious	None	None	None	None	I
A/N	0.9271	likely_pathogenic	0.9441	pathogenic	-1.359	Destabilizing	0.999	D	0.745	deleterious	None	None	None	None	I
A/P	0.9541	likely_pathogenic	0.951	pathogenic	0.111	Stabilizing	0.999	D	0.783	deleterious	D	0.627538996	None	None	I
A/Q	0.9268	likely_pathogenic	0.9462	pathogenic	-1.146	Destabilizing	0.999	D	0.747	deleterious	None	None	None	None	I
A/R	0.9448	likely_pathogenic	0.9574	pathogenic	-1.228	Destabilizing	0.999	D	0.757	deleterious	None	None	None	None	I
A/S	0.2436	likely_benign	0.2565	benign	-1.743	Destabilizing	0.989	D	0.58	neutral	D	0.570971937	None	None	I
A/T	0.2671	likely_benign	0.3005	benign	-1.406	Destabilizing	0.978	D	0.593	neutral	N	0.504387442	None	None	I
A/V	0.2744	likely_benign	0.2904	benign	0.111	Stabilizing	0.198	N	0.275	neutral	N	0.437434602	None	None	I
A/W	0.9917	likely_pathogenic	0.9931	pathogenic	-1.377	Destabilizing	1.0	D	0.746	deleterious	None	None	None	None	I
A/Y	0.9601	likely_pathogenic	0.9707	pathogenic	-0.71	Destabilizing	0.999	D	0.75	deleterious	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.