TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7078	21457;21458;21459	chr2:178724027;178724026;178724025	chr2:179588754;179588753;179588752
N2AB	6761	20506;20507;20508	chr2:178724027;178724026;178724025	chr2:179588754;179588753;179588752
N2A	5834	17725;17726;17727	chr2:178724027;178724026;178724025	chr2:179588754;179588753;179588752
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: TTT
• RefSeq wild type template codon: AAA
• Domain: Ig-55
• Domain position: 35
• Structural Position: 49
• Q(SASA): 0.1454
• 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	0.026	N	0.309	0.213	0.206339911435	gnomAD-4.0.0	1.5919E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43291E-05	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	0.8656	likely_pathogenic	0.8749	pathogenic	-2.551	Highly Destabilizing	0.919	D	0.624	neutral	None	None	None	None	N
F/C	0.6861	likely_pathogenic	0.682	pathogenic	-1.468	Destabilizing	0.999	D	0.731	prob.delet.	N	0.501627996	None	None	N
F/D	0.9144	likely_pathogenic	0.9332	pathogenic	-1.79	Destabilizing	0.996	D	0.766	deleterious	None	None	None	None	N
F/E	0.888	likely_pathogenic	0.9159	pathogenic	-1.687	Destabilizing	0.996	D	0.751	deleterious	None	None	None	None	N
F/G	0.9182	likely_pathogenic	0.9214	pathogenic	-2.904	Highly Destabilizing	0.996	D	0.739	prob.delet.	None	None	None	None	N
F/H	0.5978	likely_pathogenic	0.6229	pathogenic	-1.189	Destabilizing	0.988	D	0.666	neutral	None	None	None	None	N
F/I	0.4104	ambiguous	0.4531	ambiguous	-1.462	Destabilizing	0.811	D	0.498	neutral	N	0.459036703	None	None	N
F/K	0.8831	likely_pathogenic	0.906	pathogenic	-1.374	Destabilizing	0.988	D	0.749	deleterious	None	None	None	None	N
F/L	0.915	likely_pathogenic	0.9189	pathogenic	-1.462	Destabilizing	0.026	N	0.309	neutral	N	0.449570503	None	None	N
F/M	0.7112	likely_pathogenic	0.7354	pathogenic	-1.199	Destabilizing	0.976	D	0.556	neutral	None	None	None	None	N
F/N	0.7359	likely_pathogenic	0.7821	pathogenic	-1.444	Destabilizing	0.996	D	0.764	deleterious	None	None	None	None	N
F/P	0.9992	likely_pathogenic	0.9992	pathogenic	-1.823	Destabilizing	0.996	D	0.765	deleterious	None	None	None	None	N
F/Q	0.8338	likely_pathogenic	0.8564	pathogenic	-1.586	Destabilizing	0.996	D	0.768	deleterious	None	None	None	None	N
F/R	0.7976	likely_pathogenic	0.8225	pathogenic	-0.665	Destabilizing	0.988	D	0.762	deleterious	None	None	None	None	N
F/S	0.6446	likely_pathogenic	0.6754	pathogenic	-2.243	Highly Destabilizing	0.984	D	0.711	prob.delet.	N	0.456163094	None	None	N
F/T	0.7667	likely_pathogenic	0.8087	pathogenic	-2.046	Highly Destabilizing	0.988	D	0.708	prob.delet.	None	None	None	None	N
F/V	0.4855	ambiguous	0.5162	ambiguous	-1.823	Destabilizing	0.811	D	0.559	neutral	N	0.465620069	None	None	N
F/W	0.4988	ambiguous	0.4921	ambiguous	-0.505	Destabilizing	0.999	D	0.558	neutral	None	None	None	None	N
F/Y	0.1181	likely_benign	0.1229	benign	-0.727	Destabilizing	0.046	N	0.217	neutral	N	0.42255726	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.