TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26471	79636;79637;79638	chr2:178566721;178566720;178566719	chr2:179431448;179431447;179431446
N2AB	24830	74713;74714;74715	chr2:178566721;178566720;178566719	chr2:179431448;179431447;179431446
N2A	23903	71932;71933;71934	chr2:178566721;178566720;178566719	chr2:179431448;179431447;179431446
N2B	17406	52441;52442;52443	chr2:178566721;178566720;178566719	chr2:179431448;179431447;179431446
Novex-1	17531	52816;52817;52818	chr2:178566721;178566720;178566719	chr2:179431448;179431447;179431446
Novex-2	17598	53017;53018;53019	chr2:178566721;178566720;178566719	chr2:179431448;179431447;179431446
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-80
• Domain position: 86
• Structural Position: 119
• Q(SASA): 0.7922
• 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
E/G	None	None	0.92	N	0.509	0.341	0.363158594168	gnomAD-4.0.0	1.59201E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	0	3.02572E-05
E/K	None	None	0.704	D	0.441	0.204	0.264547087235	gnomAD-4.0.0	3.60099E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	3.93751E-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
E/A	0.1209	likely_benign	0.118	benign	-0.49	Destabilizing	0.704	D	0.472	neutral	N	0.504954931	None	None	I
E/C	0.7275	likely_pathogenic	0.7165	pathogenic	-0.096	Destabilizing	0.999	D	0.485	neutral	None	None	None	None	I
E/D	0.0962	likely_benign	0.097	benign	-0.426	Destabilizing	0.826	D	0.425	neutral	N	0.487601321	None	None	I
E/F	0.5926	likely_pathogenic	0.5942	pathogenic	-0.366	Destabilizing	0.982	D	0.488	neutral	None	None	None	None	I
E/G	0.1561	likely_benign	0.1704	benign	-0.69	Destabilizing	0.92	D	0.509	neutral	N	0.500651534	None	None	I
E/H	0.4015	ambiguous	0.4163	ambiguous	-0.18	Destabilizing	0.991	D	0.503	neutral	None	None	None	None	I
E/I	0.2007	likely_benign	0.1968	benign	0.008	Stabilizing	0.964	D	0.506	neutral	None	None	None	None	I
E/K	0.1181	likely_benign	0.1354	benign	0.228	Stabilizing	0.704	D	0.441	neutral	D	0.524791486	None	None	I
E/L	0.2097	likely_benign	0.2136	benign	0.008	Stabilizing	0.046	N	0.319	neutral	None	None	None	None	I
E/M	0.2863	likely_benign	0.2819	benign	0.144	Stabilizing	0.982	D	0.503	neutral	None	None	None	None	I
E/N	0.1946	likely_benign	0.1906	benign	-0.098	Destabilizing	0.939	D	0.509	neutral	None	None	None	None	I
E/P	0.2743	likely_benign	0.2678	benign	-0.138	Destabilizing	0.991	D	0.545	neutral	None	None	None	None	I
E/Q	0.1124	likely_benign	0.12	benign	-0.067	Destabilizing	0.31	N	0.127	neutral	N	0.493815218	None	None	I
E/R	0.2272	likely_benign	0.2539	benign	0.426	Stabilizing	0.939	D	0.518	neutral	None	None	None	None	I
E/S	0.1594	likely_benign	0.1599	benign	-0.255	Destabilizing	0.373	N	0.185	neutral	None	None	None	None	I
E/T	0.1744	likely_benign	0.1683	benign	-0.092	Destabilizing	0.884	D	0.498	neutral	None	None	None	None	I
E/V	0.1288	likely_benign	0.1287	benign	-0.138	Destabilizing	0.852	D	0.521	neutral	N	0.484575195	None	None	I
E/W	0.8663	likely_pathogenic	0.8704	pathogenic	-0.2	Destabilizing	0.999	D	0.555	neutral	None	None	None	None	I
E/Y	0.49	ambiguous	0.4878	ambiguous	-0.124	Destabilizing	0.997	D	0.501	neutral	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.