TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18794	56605;56606;56607	chr2:178599413;178599412;178599411	chr2:179464140;179464139;179464138
N2AB	17153	51682;51683;51684	chr2:178599413;178599412;178599411	chr2:179464140;179464139;179464138
N2A	16226	48901;48902;48903	chr2:178599413;178599412;178599411	chr2:179464140;179464139;179464138
N2B	9729	29410;29411;29412	chr2:178599413;178599412;178599411	chr2:179464140;179464139;179464138
Novex-1	9854	29785;29786;29787	chr2:178599413;178599412;178599411	chr2:179464140;179464139;179464138
Novex-2	9921	29986;29987;29988	chr2:178599413;178599412;178599411	chr2:179464140;179464139;179464138
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: F
• RefSeq wild type transcript codon: TTT
• RefSeq wild type template codon: AAA
• Domain: Fn3-24
• Domain position: 11
• Structural Position: 12
• Q(SASA): 0.178
• 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/V	rs757869355	-1.747	0.698	N	0.615	0.314	0.435371449458	gnomAD-2.1.1	4.94E-06	None	None	None	None	N	None	0	0	None	0	0	None	5.04E-05	None	0	0	0
F/Y	rs750336579	-0.614	0.966	N	0.637	0.312	0.424549175451	gnomAD-2.1.1	4.92E-06	None	None	None	None	N	None	0	0	None	0	0	None	5.01E-05	None	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	0.8502	likely_pathogenic	0.8072	pathogenic	-2.42	Highly Destabilizing	0.754	D	0.659	neutral	None	None	None	None	N
F/C	0.7095	likely_pathogenic	0.6667	pathogenic	-1.494	Destabilizing	0.997	D	0.761	deleterious	N	0.500743977	None	None	N
F/D	0.9838	likely_pathogenic	0.9762	pathogenic	-1.016	Destabilizing	0.956	D	0.794	deleterious	None	None	None	None	N
F/E	0.9782	likely_pathogenic	0.968	pathogenic	-0.903	Destabilizing	0.956	D	0.784	deleterious	None	None	None	None	N
F/G	0.9553	likely_pathogenic	0.9389	pathogenic	-2.79	Highly Destabilizing	0.754	D	0.756	deleterious	None	None	None	None	N
F/H	0.9192	likely_pathogenic	0.8919	pathogenic	-0.946	Destabilizing	0.998	D	0.699	prob.neutral	None	None	None	None	N
F/I	0.3073	likely_benign	0.2701	benign	-1.292	Destabilizing	0.058	N	0.398	neutral	N	0.428379659	None	None	N
F/K	0.9592	likely_pathogenic	0.9315	pathogenic	-1.523	Destabilizing	0.956	D	0.791	deleterious	None	None	None	None	N
F/L	0.9102	likely_pathogenic	0.8908	pathogenic	-1.292	Destabilizing	0.489	N	0.517	neutral	N	0.462761592	None	None	N
F/M	0.6021	likely_pathogenic	0.5512	ambiguous	-1.042	Destabilizing	0.978	D	0.589	neutral	None	None	None	None	N
F/N	0.9418	likely_pathogenic	0.9181	pathogenic	-1.603	Destabilizing	0.956	D	0.8	deleterious	None	None	None	None	N
F/P	0.9766	likely_pathogenic	0.9677	pathogenic	-1.664	Destabilizing	0.978	D	0.809	deleterious	None	None	None	None	N
F/Q	0.9564	likely_pathogenic	0.9362	pathogenic	-1.635	Destabilizing	0.956	D	0.805	deleterious	None	None	None	None	N
F/R	0.9333	likely_pathogenic	0.9005	pathogenic	-0.86	Destabilizing	0.956	D	0.817	deleterious	None	None	None	None	N
F/S	0.8855	likely_pathogenic	0.8477	pathogenic	-2.479	Highly Destabilizing	0.058	N	0.465	neutral	N	0.485678059	None	None	N
F/T	0.8337	likely_pathogenic	0.7797	pathogenic	-2.262	Highly Destabilizing	0.754	D	0.734	prob.delet.	None	None	None	None	N
F/V	0.4198	ambiguous	0.3697	ambiguous	-1.664	Destabilizing	0.698	D	0.615	neutral	N	0.425797927	None	None	N
F/W	0.6063	likely_pathogenic	0.5817	pathogenic	-0.37	Destabilizing	0.998	D	0.603	neutral	None	None	None	None	N
F/Y	0.3326	likely_benign	0.2996	benign	-0.681	Destabilizing	0.966	D	0.637	neutral	N	0.502802847	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.