TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5749	17470;17471;17472	chr2:178731521;178731520;178731519	chr2:179596248;179596247;179596246
N2AB	5432	16519;16520;16521	chr2:178731521;178731520;178731519	chr2:179596248;179596247;179596246
N2A	4505	13738;13739;13740	chr2:178731521;178731520;178731519	chr2:179596248;179596247;179596246
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: F
• RefSeq wild type transcript codon: TTC
• RefSeq wild type template codon: AAG
• Domain: Ig-41
• Domain position: 20
• Structural Position: 30
• Q(SASA): 0.1112
• 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
F/C	None	None	0.999	D	0.839	0.837	0.878891999469	gnomAD-4.0.0	1.59236E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85979E-06	0	0
F/L	rs562519092	-0.687	0.005	N	0.281	0.282	0.37953744168	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	1.93125E-04	None	0	0	0	0	0
F/L	rs562519092	-0.687	0.005	N	0.281	0.282	0.37953744168	1000 genomes	1.99681E-04	None	None	None	None	N	None	0	0	None	None	1E-03	0	None	None	None	0	None
F/L	rs562519092	-0.687	0.005	N	0.281	0.282	0.37953744168	gnomAD-4.0.0	6.56797E-06	None	None	None	None	N	None	0	0	None	0	1.93573E-04	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
F/A	0.991	likely_pathogenic	0.9892	pathogenic	-2.092	Highly Destabilizing	0.863	D	0.725	prob.delet.	None	None	None	None	N
F/C	0.9445	likely_pathogenic	0.9435	pathogenic	-1.368	Destabilizing	0.999	D	0.839	deleterious	D	0.580839812	None	None	N
F/D	0.9996	likely_pathogenic	0.9993	pathogenic	-2.999	Highly Destabilizing	0.997	D	0.833	deleterious	None	None	None	None	N
F/E	0.9992	likely_pathogenic	0.9988	pathogenic	-2.745	Highly Destabilizing	0.997	D	0.798	deleterious	None	None	None	None	N
F/G	0.9968	likely_pathogenic	0.9955	pathogenic	-2.566	Highly Destabilizing	0.99	D	0.787	deleterious	None	None	None	None	N
F/H	0.9938	likely_pathogenic	0.9914	pathogenic	-1.744	Destabilizing	0.999	D	0.763	deleterious	None	None	None	None	N
F/I	0.7038	likely_pathogenic	0.6977	pathogenic	-0.541	Destabilizing	0.704	D	0.541	neutral	N	0.495849272	None	None	N
F/K	0.999	likely_pathogenic	0.9983	pathogenic	-1.889	Destabilizing	0.997	D	0.802	deleterious	None	None	None	None	N
F/L	0.9091	likely_pathogenic	0.9062	pathogenic	-0.541	Destabilizing	0.005	N	0.281	neutral	N	0.444629696	None	None	N
F/M	0.8319	likely_pathogenic	0.8247	pathogenic	-0.451	Destabilizing	0.982	D	0.646	neutral	None	None	None	None	N
F/N	0.9978	likely_pathogenic	0.9969	pathogenic	-2.597	Highly Destabilizing	0.997	D	0.84	deleterious	None	None	None	None	N
F/P	0.9998	likely_pathogenic	0.9997	pathogenic	-1.072	Destabilizing	0.997	D	0.843	deleterious	None	None	None	None	N
F/Q	0.9976	likely_pathogenic	0.9965	pathogenic	-2.317	Highly Destabilizing	0.997	D	0.849	deleterious	None	None	None	None	N
F/R	0.9971	likely_pathogenic	0.9956	pathogenic	-1.929	Destabilizing	0.997	D	0.843	deleterious	None	None	None	None	N
F/S	0.994	likely_pathogenic	0.992	pathogenic	-3.056	Highly Destabilizing	0.959	D	0.747	deleterious	D	0.580839812	None	None	N
F/T	0.9951	likely_pathogenic	0.9934	pathogenic	-2.666	Highly Destabilizing	0.939	D	0.727	prob.delet.	None	None	None	None	N
F/V	0.7915	likely_pathogenic	0.7898	pathogenic	-1.072	Destabilizing	0.061	N	0.527	neutral	N	0.49686323	None	None	N
F/W	0.9242	likely_pathogenic	0.9123	pathogenic	-0.003	Destabilizing	0.999	D	0.629	neutral	None	None	None	None	N
F/Y	0.6863	likely_pathogenic	0.6784	pathogenic	-0.372	Destabilizing	0.986	D	0.589	neutral	D	0.580638008	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.