TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	34193	102802;102803;102804	chr2:178534038;178534037;178534036	chr2:179398765;179398764;179398763
N2AB	32552	97879;97880;97881	chr2:178534038;178534037;178534036	chr2:179398765;179398764;179398763
N2A	31625	95098;95099;95100	chr2:178534038;178534037;178534036	chr2:179398765;179398764;179398763
N2B	25128	75607;75608;75609	chr2:178534038;178534037;178534036	chr2:179398765;179398764;179398763
Novex-1	25253	75982;75983;75984	chr2:178534038;178534037;178534036	chr2:179398765;179398764;179398763
Novex-2	25320	76183;76184;76185	chr2:178534038;178534037;178534036	chr2:179398765;179398764;179398763
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Ig-160
• Domain position: 57
• Structural Position: 137
• Q(SASA): 0.2514
• 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/F	None	None	0.065	N	0.47	0.162	0.582419091513	gnomAD-4.0.0	1.59098E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85767E-06	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
I/A	0.17	likely_benign	0.1673	benign	-2.354	Highly Destabilizing	0.002	N	0.331	neutral	None	None	None	None	N
I/C	0.4862	ambiguous	0.5206	ambiguous	-1.468	Destabilizing	0.245	N	0.526	neutral	None	None	None	None	N
I/D	0.5648	likely_pathogenic	0.6067	pathogenic	-2.728	Highly Destabilizing	0.018	N	0.503	neutral	None	None	None	None	N
I/E	0.3701	ambiguous	0.3878	ambiguous	-2.511	Highly Destabilizing	0.018	N	0.508	neutral	None	None	None	None	N
I/F	0.1484	likely_benign	0.1557	benign	-1.419	Destabilizing	0.065	N	0.47	neutral	N	0.502331205	None	None	N
I/G	0.5417	ambiguous	0.567	pathogenic	-2.879	Highly Destabilizing	0.004	N	0.498	neutral	None	None	None	None	N
I/H	0.2898	likely_benign	0.3107	benign	-2.416	Highly Destabilizing	0.497	N	0.581	neutral	None	None	None	None	N
I/K	0.2192	likely_benign	0.2362	benign	-1.837	Destabilizing	0.018	N	0.505	neutral	None	None	None	None	N
I/L	0.1141	likely_benign	0.1178	benign	-0.842	Destabilizing	0.001	N	0.292	neutral	N	0.49434644	None	None	N
I/M	0.0877	likely_benign	0.0889	benign	-0.694	Destabilizing	0.196	N	0.517	neutral	N	0.513721635	None	None	N
I/N	0.1555	likely_benign	0.1719	benign	-2.148	Highly Destabilizing	0.014	N	0.501	neutral	N	0.488420546	None	None	N
I/P	0.9355	likely_pathogenic	0.9461	pathogenic	-1.327	Destabilizing	0.085	N	0.537	neutral	None	None	None	None	N
I/Q	0.2702	likely_benign	0.2889	benign	-2.022	Highly Destabilizing	0.085	N	0.586	neutral	None	None	None	None	N
I/R	0.1616	likely_benign	0.1739	benign	-1.546	Destabilizing	0.044	N	0.554	neutral	None	None	None	None	N
I/S	0.1303	likely_benign	0.1333	benign	-2.789	Highly Destabilizing	None	N	0.309	neutral	N	0.404916515	None	None	N
I/T	0.0613	likely_benign	0.0612	benign	-2.436	Highly Destabilizing	None	N	0.239	neutral	N	0.424480923	None	None	N
I/V	0.0724	likely_benign	0.0739	benign	-1.327	Destabilizing	None	N	0.135	neutral	N	0.429969675	None	None	N
I/W	0.6558	likely_pathogenic	0.6913	pathogenic	-1.879	Destabilizing	0.788	D	0.598	neutral	None	None	None	None	N
I/Y	0.3115	likely_benign	0.3238	benign	-1.542	Destabilizing	0.085	N	0.566	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.