TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27986	84181;84182;84183	chr2:178562176;178562175;178562174	chr2:179426903;179426902;179426901
N2AB	26345	79258;79259;79260	chr2:178562176;178562175;178562174	chr2:179426903;179426902;179426901
N2A	25418	76477;76478;76479	chr2:178562176;178562175;178562174	chr2:179426903;179426902;179426901
N2B	18921	56986;56987;56988	chr2:178562176;178562175;178562174	chr2:179426903;179426902;179426901
Novex-1	19046	57361;57362;57363	chr2:178562176;178562175;178562174	chr2:179426903;179426902;179426901
Novex-2	19113	57562;57563;57564	chr2:178562176;178562175;178562174	chr2:179426903;179426902;179426901
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-142
• Domain position: 24
• Structural Position: 35
• Q(SASA): 0.1683
• 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	rs1184136352	-1.774	0.027	N	0.603	0.195	0.257786959452	gnomAD-2.1.1	4.05E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.95E-06	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	0.8352	likely_pathogenic	0.8391	pathogenic	-2.979	Highly Destabilizing	0.081	N	0.678	prob.neutral	None	None	None	None	N
F/C	0.3776	ambiguous	0.3695	ambiguous	-1.948	Destabilizing	0.915	D	0.743	deleterious	N	0.488263677	None	None	N
F/D	0.9891	likely_pathogenic	0.99	pathogenic	-2.876	Highly Destabilizing	0.38	N	0.805	deleterious	None	None	None	None	N
F/E	0.9828	likely_pathogenic	0.9842	pathogenic	-2.723	Highly Destabilizing	0.555	D	0.805	deleterious	None	None	None	None	N
F/G	0.9505	likely_pathogenic	0.9521	pathogenic	-3.376	Highly Destabilizing	0.001	N	0.491	neutral	None	None	None	None	N
F/H	0.8502	likely_pathogenic	0.8393	pathogenic	-1.703	Destabilizing	0.38	N	0.749	deleterious	None	None	None	None	N
F/I	0.1911	likely_benign	0.1935	benign	-1.704	Destabilizing	0.001	N	0.431	neutral	N	0.466578262	None	None	N
F/K	0.9714	likely_pathogenic	0.9721	pathogenic	-1.915	Destabilizing	0.38	N	0.805	deleterious	None	None	None	None	N
F/L	0.8482	likely_pathogenic	0.8533	pathogenic	-1.704	Destabilizing	0.027	N	0.603	neutral	N	0.488944786	None	None	N
F/M	0.5818	likely_pathogenic	0.5984	pathogenic	-1.53	Destabilizing	0.38	N	0.667	neutral	None	None	None	None	N
F/N	0.9538	likely_pathogenic	0.9522	pathogenic	-2.159	Highly Destabilizing	0.38	N	0.805	deleterious	None	None	None	None	N
F/P	0.9943	likely_pathogenic	0.9945	pathogenic	-2.135	Highly Destabilizing	0.791	D	0.804	deleterious	None	None	None	None	N
F/Q	0.9467	likely_pathogenic	0.95	pathogenic	-2.242	Highly Destabilizing	0.555	D	0.799	deleterious	None	None	None	None	N
F/R	0.9359	likely_pathogenic	0.9395	pathogenic	-1.243	Destabilizing	0.38	N	0.805	deleterious	None	None	None	None	N
F/S	0.8276	likely_pathogenic	0.8267	pathogenic	-2.88	Highly Destabilizing	0.117	N	0.754	deleterious	D	0.534366266	None	None	N
F/T	0.8405	likely_pathogenic	0.8391	pathogenic	-2.626	Highly Destabilizing	0.38	N	0.775	deleterious	None	None	None	None	N
F/V	0.1963	likely_benign	0.2004	benign	-2.135	Highly Destabilizing	0.062	N	0.66	neutral	N	0.427590226	None	None	N
F/W	0.575	likely_pathogenic	0.5841	pathogenic	-0.502	Destabilizing	0.824	D	0.655	neutral	None	None	None	None	N
F/Y	0.1987	likely_benign	0.1989	benign	-0.865	Destabilizing	None	N	0.305	neutral	N	0.508142457	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.