TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23899	71920;71921;71922	chr2:178574437;178574436;178574435	chr2:179439164;179439163;179439162
N2AB	22258	66997;66998;66999	chr2:178574437;178574436;178574435	chr2:179439164;179439163;179439162
N2A	21331	64216;64217;64218	chr2:178574437;178574436;178574435	chr2:179439164;179439163;179439162
N2B	14834	44725;44726;44727	chr2:178574437;178574436;178574435	chr2:179439164;179439163;179439162
Novex-1	14959	45100;45101;45102	chr2:178574437;178574436;178574435	chr2:179439164;179439163;179439162
Novex-2	15026	45301;45302;45303	chr2:178574437;178574436;178574435	chr2:179439164;179439163;179439162
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: Fn3-61
• Domain position: 74
• Structural Position: 106
• Q(SASA): 0.1382
• 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/L	None	None	0.98	N	0.711	0.424	0.624499334446	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-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
F/A	0.9958	likely_pathogenic	0.9922	pathogenic	-3.232	Highly Destabilizing	0.993	D	0.808	deleterious	None	None	None	None	N
F/C	0.9185	likely_pathogenic	0.871	pathogenic	-1.694	Destabilizing	1.0	D	0.821	deleterious	D	0.552569032	None	None	N
F/D	0.9984	likely_pathogenic	0.9975	pathogenic	-3.859	Highly Destabilizing	0.998	D	0.85	deleterious	None	None	None	None	N
F/E	0.9989	likely_pathogenic	0.9982	pathogenic	-3.633	Highly Destabilizing	0.996	D	0.817	deleterious	None	None	None	None	N
F/G	0.9969	likely_pathogenic	0.9939	pathogenic	-3.667	Highly Destabilizing	0.998	D	0.822	deleterious	None	None	None	None	N
F/H	0.8525	likely_pathogenic	0.8397	pathogenic	-2.326	Highly Destabilizing	0.323	N	0.639	neutral	None	None	None	None	N
F/I	0.9384	likely_pathogenic	0.9056	pathogenic	-1.777	Destabilizing	0.997	D	0.734	prob.delet.	N	0.50189621	None	None	N
F/K	0.999	likely_pathogenic	0.9984	pathogenic	-2.455	Highly Destabilizing	0.998	D	0.847	deleterious	None	None	None	None	N
F/L	0.9926	likely_pathogenic	0.9886	pathogenic	-1.777	Destabilizing	0.98	D	0.711	prob.delet.	N	0.504809499	None	None	N
F/M	0.957	likely_pathogenic	0.9397	pathogenic	-1.293	Destabilizing	1.0	D	0.722	prob.delet.	None	None	None	None	N
F/N	0.9836	likely_pathogenic	0.9767	pathogenic	-3.062	Highly Destabilizing	0.996	D	0.85	deleterious	None	None	None	None	N
F/P	0.9999	likely_pathogenic	0.9998	pathogenic	-2.279	Highly Destabilizing	0.999	D	0.865	deleterious	None	None	None	None	N
F/Q	0.9964	likely_pathogenic	0.9945	pathogenic	-2.973	Highly Destabilizing	0.998	D	0.861	deleterious	None	None	None	None	N
F/R	0.9978	likely_pathogenic	0.9964	pathogenic	-2.007	Highly Destabilizing	0.996	D	0.851	deleterious	None	None	None	None	N
F/S	0.9908	likely_pathogenic	0.9828	pathogenic	-3.547	Highly Destabilizing	0.997	D	0.821	deleterious	D	0.564089922	None	None	N
F/T	0.9952	likely_pathogenic	0.9915	pathogenic	-3.213	Highly Destabilizing	0.998	D	0.809	deleterious	None	None	None	None	N
F/V	0.947	likely_pathogenic	0.9159	pathogenic	-2.279	Highly Destabilizing	0.98	D	0.775	deleterious	N	0.497106362	None	None	N
F/W	0.7263	likely_pathogenic	0.695	pathogenic	-0.79	Destabilizing	1.0	D	0.723	prob.delet.	None	None	None	None	N
F/Y	0.2211	likely_benign	0.2213	benign	-1.253	Destabilizing	0.4	N	0.263	neutral	N	0.497153404	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.