TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25041	75346;75347;75348	chr2:178571011;178571010;178571009	chr2:179435738;179435737;179435736
N2AB	23400	70423;70424;70425	chr2:178571011;178571010;178571009	chr2:179435738;179435737;179435736
N2A	22473	67642;67643;67644	chr2:178571011;178571010;178571009	chr2:179435738;179435737;179435736
N2B	15976	48151;48152;48153	chr2:178571011;178571010;178571009	chr2:179435738;179435737;179435736
Novex-1	16101	48526;48527;48528	chr2:178571011;178571010;178571009	chr2:179435738;179435737;179435736
Novex-2	16168	48727;48728;48729	chr2:178571011;178571010;178571009	chr2:179435738;179435737;179435736
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Fn3-70
• Domain position: 36
• Structural Position: 38
• Q(SASA): 0.1166
• 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
Y/C	rs375688406	-1.946	1.0	D	0.863	0.822	None	gnomAD-3.1.2	1.97E-05	None	None	None	None	N	None	7.24E-05	0	0	0	0	None	0	0	0	0	0
Y/C	rs375688406	-1.946	1.0	D	0.863	0.822	None	gnomAD-4.0.0	4.06038E-06	None	None	None	None	N	None	6.99276E-05	0	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
Y/A	0.998	likely_pathogenic	0.9976	pathogenic	-3.404	Highly Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
Y/C	0.9355	likely_pathogenic	0.9281	pathogenic	-1.789	Destabilizing	1.0	D	0.863	deleterious	D	0.654375286	None	None	N
Y/D	0.9976	likely_pathogenic	0.9971	pathogenic	-3.829	Highly Destabilizing	1.0	D	0.903	deleterious	D	0.65457709	None	None	N
Y/E	0.9993	likely_pathogenic	0.9992	pathogenic	-3.606	Highly Destabilizing	1.0	D	0.899	deleterious	None	None	None	None	N
Y/F	0.3031	likely_benign	0.2871	benign	-1.378	Destabilizing	0.999	D	0.649	neutral	N	0.511254047	None	None	N
Y/G	0.9929	likely_pathogenic	0.9923	pathogenic	-3.816	Highly Destabilizing	1.0	D	0.922	deleterious	None	None	None	None	N
Y/H	0.9876	likely_pathogenic	0.985	pathogenic	-2.625	Highly Destabilizing	1.0	D	0.822	deleterious	D	0.637921956	None	None	N
Y/I	0.9841	likely_pathogenic	0.9791	pathogenic	-2.008	Highly Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
Y/K	0.9994	likely_pathogenic	0.9992	pathogenic	-2.426	Highly Destabilizing	1.0	D	0.895	deleterious	None	None	None	None	N
Y/L	0.9615	likely_pathogenic	0.9539	pathogenic	-2.008	Highly Destabilizing	0.999	D	0.741	deleterious	None	None	None	None	N
Y/M	0.9877	likely_pathogenic	0.9854	pathogenic	-1.707	Destabilizing	1.0	D	0.84	deleterious	None	None	None	None	N
Y/N	0.9809	likely_pathogenic	0.9788	pathogenic	-3.261	Highly Destabilizing	1.0	D	0.883	deleterious	D	0.65457709	None	None	N
Y/P	0.9995	likely_pathogenic	0.9995	pathogenic	-2.493	Highly Destabilizing	1.0	D	0.926	deleterious	None	None	None	None	N
Y/Q	0.9991	likely_pathogenic	0.9989	pathogenic	-2.97	Highly Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
Y/R	0.9973	likely_pathogenic	0.9969	pathogenic	-2.262	Highly Destabilizing	1.0	D	0.878	deleterious	None	None	None	None	N
Y/S	0.9909	likely_pathogenic	0.99	pathogenic	-3.527	Highly Destabilizing	1.0	D	0.898	deleterious	D	0.638325564	None	None	N
Y/T	0.9976	likely_pathogenic	0.997	pathogenic	-3.182	Highly Destabilizing	1.0	D	0.899	deleterious	None	None	None	None	N
Y/V	0.9736	likely_pathogenic	0.9658	pathogenic	-2.493	Highly Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	N
Y/W	0.8786	likely_pathogenic	0.8813	pathogenic	-0.634	Destabilizing	1.0	D	0.799	deleterious	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.