TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7166	21721;21722;21723	chr2:178723604;178723603;178723602	chr2:179588331;179588330;179588329
N2AB	6849	20770;20771;20772	chr2:178723604;178723603;178723602	chr2:179588331;179588330;179588329
N2A	5922	17989;17990;17991	chr2:178723604;178723603;178723602	chr2:179588331;179588330;179588329
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-56
• Domain position: 30
• Structural Position: 44
• Q(SASA): 0.1524
• 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	rs781740874	-1.555	0.997	N	0.593	0.517	0.809359663723	gnomAD-2.1.1	1.61E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	3.57E-05	0
F/C	rs781740874	-1.555	0.997	N	0.593	0.517	0.809359663723	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
F/C	rs781740874	-1.555	0.997	N	0.593	0.517	0.809359663723	gnomAD-4.0.0	5.57935E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	6.78229E-06	0	1.60231E-05

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	0.7927	likely_pathogenic	0.8071	pathogenic	-2.716	Highly Destabilizing	0.688	D	0.501	neutral	None	None	None	None	N
F/C	0.4455	ambiguous	0.4648	ambiguous	-1.842	Destabilizing	0.997	D	0.593	neutral	N	0.514926307	None	None	N
F/D	0.9719	likely_pathogenic	0.9743	pathogenic	-2.164	Highly Destabilizing	0.991	D	0.679	prob.neutral	None	None	None	None	N
F/E	0.9644	likely_pathogenic	0.9666	pathogenic	-1.974	Destabilizing	0.991	D	0.676	prob.neutral	None	None	None	None	N
F/G	0.9129	likely_pathogenic	0.923	pathogenic	-3.156	Highly Destabilizing	0.915	D	0.663	neutral	None	None	None	None	N
F/H	0.8422	likely_pathogenic	0.8516	pathogenic	-1.47	Destabilizing	0.998	D	0.604	neutral	None	None	None	None	N
F/I	0.3347	likely_benign	0.3618	ambiguous	-1.312	Destabilizing	0.454	N	0.479	neutral	N	0.507467666	None	None	N
F/K	0.9478	likely_pathogenic	0.9557	pathogenic	-2.017	Highly Destabilizing	0.974	D	0.683	prob.neutral	None	None	None	None	N
F/L	0.6762	likely_pathogenic	0.7138	pathogenic	-1.312	Destabilizing	0.002	N	0.129	neutral	N	0.448552649	None	None	N
F/M	0.5273	ambiguous	0.5514	ambiguous	-1.089	Destabilizing	0.325	N	0.347	neutral	None	None	None	None	N
F/N	0.9108	likely_pathogenic	0.9184	pathogenic	-2.318	Highly Destabilizing	0.991	D	0.687	prob.neutral	None	None	None	None	N
F/P	0.9694	likely_pathogenic	0.9712	pathogenic	-1.786	Destabilizing	0.991	D	0.687	prob.neutral	None	None	None	None	N
F/Q	0.9073	likely_pathogenic	0.9162	pathogenic	-2.262	Highly Destabilizing	0.974	D	0.686	prob.neutral	None	None	None	None	N
F/R	0.8847	likely_pathogenic	0.901	pathogenic	-1.497	Destabilizing	0.974	D	0.675	prob.neutral	None	None	None	None	N
F/S	0.7747	likely_pathogenic	0.7887	pathogenic	-3.125	Highly Destabilizing	0.891	D	0.603	neutral	N	0.512470841	None	None	N
F/T	0.8609	likely_pathogenic	0.87	pathogenic	-2.824	Highly Destabilizing	0.915	D	0.599	neutral	None	None	None	None	N
F/V	0.3072	likely_benign	0.3253	benign	-1.786	Destabilizing	0.454	N	0.504	neutral	N	0.513393561	None	None	N
F/W	0.6065	likely_pathogenic	0.5959	pathogenic	-0.215	Destabilizing	0.998	D	0.545	neutral	None	None	None	None	N
F/Y	0.2615	likely_benign	0.2535	benign	-0.625	Destabilizing	0.891	D	0.535	neutral	N	0.488174772	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.