TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9542	28849;28850;28851	chr2:178709695;178709694;178709693	chr2:179574422;179574421;179574420
N2AB	9225	27898;27899;27900	chr2:178709695;178709694;178709693	chr2:179574422;179574421;179574420
N2A	8298	25117;25118;25119	chr2:178709695;178709694;178709693	chr2:179574422;179574421;179574420
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: I
• RefSeq wild type transcript codon: ATA
• RefSeq wild type template codon: TAT
• Domain: Ig-81
• Domain position: 50
• Structural Position: 123
• Q(SASA): 0.3876
• 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
I/V	rs1474085210	-1.069	None	None	0.102	0.093	0.343101102393	gnomAD-2.1.1	1.61E-05	None	None	None	None	N	None	0	5.8E-05	None	0	5.56E-05	None	0	None	0	8.85E-06	0
I/V	rs1474085210	-1.069	None	None	0.102	0.093	0.343101102393	gnomAD-3.1.2	3.94E-05	None	None	None	None	N	None	0	3.92773E-04	0	0	0	None	0	0	0	0	0
I/V	rs1474085210	-1.069	None	None	0.102	0.093	0.343101102393	gnomAD-4.0.0	9.91435E-06	None	None	None	None	N	None	0	1.33351E-04	None	0	1.55944E-04	None	0	0	0	0	1.60097E-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
I/A	0.6984	likely_pathogenic	0.6777	pathogenic	-2.132	Highly Destabilizing	0.035	N	0.445	neutral	None	None	None	None	N
I/C	0.8343	likely_pathogenic	0.8422	pathogenic	-1.242	Destabilizing	0.935	D	0.584	neutral	None	None	None	None	N
I/D	0.942	likely_pathogenic	0.9378	pathogenic	-1.94	Destabilizing	0.791	D	0.615	neutral	None	None	None	None	N
I/E	0.8622	likely_pathogenic	0.8566	pathogenic	-1.854	Destabilizing	0.555	D	0.628	neutral	None	None	None	None	N
I/F	0.2169	likely_benign	0.23	benign	-1.411	Destabilizing	0.001	N	0.269	neutral	None	None	None	None	N
I/G	0.8985	likely_pathogenic	0.8919	pathogenic	-2.554	Highly Destabilizing	0.555	D	0.617	neutral	None	None	None	None	N
I/H	0.81	likely_pathogenic	0.8061	pathogenic	-1.874	Destabilizing	0.935	D	0.603	neutral	None	None	None	None	N
I/K	0.6909	likely_pathogenic	0.6931	pathogenic	-1.593	Destabilizing	0.484	N	0.628	neutral	None	None	None	None	N
I/L	0.164	likely_benign	0.1648	benign	-0.987	Destabilizing	None	N	0.085	neutral	None	None	None	None	N
I/M	0.0973	likely_benign	0.0998	benign	-0.723	Destabilizing	0.188	N	0.521	neutral	None	None	None	None	N
I/N	0.6101	likely_pathogenic	0.6104	pathogenic	-1.52	Destabilizing	0.791	D	0.615	neutral	None	None	None	None	N
I/P	0.9544	likely_pathogenic	0.9477	pathogenic	-1.342	Destabilizing	0.791	D	0.616	neutral	None	None	None	None	N
I/Q	0.7515	likely_pathogenic	0.7499	pathogenic	-1.597	Destabilizing	0.791	D	0.617	neutral	None	None	None	None	N
I/R	0.6246	likely_pathogenic	0.6273	pathogenic	-1.075	Destabilizing	0.484	N	0.616	neutral	None	None	None	None	N
I/S	0.6991	likely_pathogenic	0.6881	pathogenic	-2.147	Highly Destabilizing	0.262	N	0.583	neutral	None	None	None	None	N
I/T	0.5667	likely_pathogenic	0.558	ambiguous	-1.933	Destabilizing	0.117	N	0.498	neutral	None	None	None	None	N
I/V	0.1148	likely_benign	0.1115	benign	-1.342	Destabilizing	None	N	0.102	neutral	None	None	None	None	N
I/W	0.8348	likely_pathogenic	0.8362	pathogenic	-1.626	Destabilizing	0.935	D	0.618	neutral	None	None	None	None	N
I/Y	0.5962	likely_pathogenic	0.6106	pathogenic	-1.382	Destabilizing	0.235	N	0.596	neutral	None	None	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.