TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30180	90763;90764;90765	chr2:178552362;178552361;178552360	chr2:179417089;179417088;179417087
N2AB	28539	85840;85841;85842	chr2:178552362;178552361;178552360	chr2:179417089;179417088;179417087
N2A	27612	83059;83060;83061	chr2:178552362;178552361;178552360	chr2:179417089;179417088;179417087
N2B	21115	63568;63569;63570	chr2:178552362;178552361;178552360	chr2:179417089;179417088;179417087
Novex-1	21240	63943;63944;63945	chr2:178552362;178552361;178552360	chr2:179417089;179417088;179417087
Novex-2	21307	64144;64145;64146	chr2:178552362;178552361;178552360	chr2:179417089;179417088;179417087
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-148
• Domain position: 49
• Structural Position: 123
• Q(SASA): 0.2208
• 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	None	N	0.147	0.124	0.249502417897	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	6.33473E-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
F/A	0.6458	likely_pathogenic	0.559	ambiguous	-2.186	Highly Destabilizing	0.149	N	0.457	neutral	None	None	None	None	N
F/C	0.3128	likely_benign	0.2698	benign	-1.593	Destabilizing	0.915	D	0.569	neutral	N	0.506065217	None	None	N
F/D	0.9152	likely_pathogenic	0.8585	pathogenic	-1.223	Destabilizing	0.555	D	0.604	neutral	None	None	None	None	N
F/E	0.8795	likely_pathogenic	0.8422	pathogenic	-1.042	Destabilizing	0.555	D	0.589	neutral	None	None	None	None	N
F/G	0.8355	likely_pathogenic	0.7823	pathogenic	-2.6	Highly Destabilizing	0.555	D	0.572	neutral	None	None	None	None	N
F/H	0.6228	likely_pathogenic	0.5575	ambiguous	-0.974	Destabilizing	0.38	N	0.503	neutral	None	None	None	None	N
F/I	0.1699	likely_benign	0.1413	benign	-0.891	Destabilizing	0.062	N	0.405	neutral	N	0.427177299	None	None	N
F/K	0.8389	likely_pathogenic	0.799	pathogenic	-1.582	Destabilizing	0.38	N	0.588	neutral	None	None	None	None	N
F/L	0.6674	likely_pathogenic	0.6794	pathogenic	-0.891	Destabilizing	None	N	0.147	neutral	N	0.48424409	None	None	N
F/M	0.3696	ambiguous	0.3856	ambiguous	-0.822	Destabilizing	0.035	N	0.335	neutral	None	None	None	None	N
F/N	0.7491	likely_pathogenic	0.6322	pathogenic	-1.879	Destabilizing	0.555	D	0.609	neutral	None	None	None	None	N
F/P	0.9672	likely_pathogenic	0.9626	pathogenic	-1.324	Destabilizing	0.791	D	0.608	neutral	None	None	None	None	N
F/Q	0.7574	likely_pathogenic	0.7251	pathogenic	-1.76	Destabilizing	0.555	D	0.611	neutral	None	None	None	None	N
F/R	0.7872	likely_pathogenic	0.7484	pathogenic	-1.199	Destabilizing	0.555	D	0.603	neutral	None	None	None	None	N
F/S	0.631	likely_pathogenic	0.5005	ambiguous	-2.718	Highly Destabilizing	0.317	N	0.537	neutral	N	0.504448791	None	None	N
F/T	0.5406	ambiguous	0.4552	ambiguous	-2.422	Highly Destabilizing	0.38	N	0.538	neutral	None	None	None	None	N
F/V	0.1965	likely_benign	0.1697	benign	-1.324	Destabilizing	0.062	N	0.425	neutral	N	0.432369688	None	None	N
F/W	0.4611	ambiguous	0.4596	ambiguous	0.058	Stabilizing	0.824	D	0.467	neutral	None	None	None	None	N
F/Y	0.1744	likely_benign	0.1271	benign	-0.293	Destabilizing	None	N	0.254	neutral	N	0.517204657	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.