TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7410	22453;22454;22455	chr2:178722671;178722670;178722669	chr2:179587398;179587397;179587396
N2AB	7093	21502;21503;21504	chr2:178722671;178722670;178722669	chr2:179587398;179587397;179587396
N2A	6166	18721;18722;18723	chr2:178722671;178722670;178722669	chr2:179587398;179587397;179587396
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-58
• Domain position: 88
• Structural Position: 174
• Q(SASA): 0.146
• 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	rs747973968	-0.601	0.002	N	0.239	0.122	0.0716867268079	gnomAD-2.1.1	4.08E-06	None	None	None	None	N	None	0	2.94E-05	None	0	0	None	0	None	0	0	0
F/L	rs747973968	-0.601	0.002	N	0.239	0.122	0.0716867268079	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	0	0	0	0	0	None	1.88466E-04	0	0	0	0
F/L	rs747973968	-0.601	0.002	N	0.239	0.122	0.0716867268079	gnomAD-4.0.0	6.86648E-07	None	None	None	None	N	None	0	2.25744E-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
F/A	0.8111	likely_pathogenic	0.9021	pathogenic	-1.821	Destabilizing	0.688	D	0.61	neutral	None	None	None	None	N
F/C	0.3598	ambiguous	0.546	ambiguous	-1.008	Destabilizing	0.997	D	0.623	neutral	N	0.490147689	None	None	N
F/D	0.9893	likely_pathogenic	0.9951	pathogenic	-2.796	Highly Destabilizing	0.991	D	0.665	neutral	None	None	None	None	N
F/E	0.9842	likely_pathogenic	0.9924	pathogenic	-2.533	Highly Destabilizing	0.991	D	0.665	neutral	None	None	None	None	N
F/G	0.9387	likely_pathogenic	0.9702	pathogenic	-2.3	Highly Destabilizing	0.971	D	0.65	neutral	None	None	None	None	N
F/H	0.925	likely_pathogenic	0.9621	pathogenic	-1.89	Destabilizing	0.998	D	0.608	neutral	None	None	None	None	N
F/I	0.1416	likely_benign	0.21	benign	-0.255	Destabilizing	0.454	N	0.503	neutral	N	0.386287029	None	None	N
F/K	0.9829	likely_pathogenic	0.9912	pathogenic	-1.583	Destabilizing	0.974	D	0.67	neutral	None	None	None	None	N
F/L	0.4955	ambiguous	0.5895	pathogenic	-0.255	Destabilizing	0.002	N	0.239	neutral	N	0.262613165	None	None	N
F/M	0.4499	ambiguous	0.5417	ambiguous	-0.199	Destabilizing	0.949	D	0.663	neutral	None	None	None	None	N
F/N	0.9641	likely_pathogenic	0.9823	pathogenic	-2.338	Highly Destabilizing	0.991	D	0.668	neutral	None	None	None	None	N
F/P	0.9878	likely_pathogenic	0.9957	pathogenic	-0.791	Destabilizing	0.991	D	0.669	neutral	None	None	None	None	N
F/Q	0.9621	likely_pathogenic	0.9802	pathogenic	-1.98	Destabilizing	0.991	D	0.677	prob.neutral	None	None	None	None	N
F/R	0.9563	likely_pathogenic	0.9764	pathogenic	-1.835	Destabilizing	0.974	D	0.673	neutral	None	None	None	None	N
F/S	0.8744	likely_pathogenic	0.946	pathogenic	-2.703	Highly Destabilizing	0.891	D	0.627	neutral	N	0.471465928	None	None	N
F/T	0.8629	likely_pathogenic	0.9325	pathogenic	-2.301	Highly Destabilizing	0.842	D	0.617	neutral	None	None	None	None	N
F/V	0.1871	likely_benign	0.2699	benign	-0.791	Destabilizing	0.022	N	0.365	neutral	N	0.330198886	None	None	N
F/W	0.6677	likely_pathogenic	0.773	pathogenic	-0.024	Destabilizing	0.998	D	0.633	neutral	None	None	None	None	N
F/Y	0.3137	likely_benign	0.4167	ambiguous	-0.353	Destabilizing	0.891	D	0.581	neutral	N	0.490147689	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.