TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8785	26578;26579;26580	chr2:178714421;178714420;178714419	chr2:179579148;179579147;179579146
N2AB	8468	25627;25628;25629	chr2:178714421;178714420;178714419	chr2:179579148;179579147;179579146
N2A	7541	22846;22847;22848	chr2:178714421;178714420;178714419	chr2:179579148;179579147;179579146
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: ATT
• RefSeq wild type template codon: TAA
• Domain: Ig-73
• Domain position: 50
• Structural Position: 123
• Q(SASA): 0.2581
• 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	rs2077149198	None	0.076	N	0.443	0.354	0.456830177556	gnomAD-4.0.0	3.18283E-06	None	None	None	None	N	None	0	2.28697E-05	None	0	0	None	0	0	2.85853E-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	0.5265	ambiguous	0.6915	pathogenic	-2.12	Highly Destabilizing	0.031	N	0.411	neutral	None	None	None	None	N
I/C	0.7084	likely_pathogenic	0.8296	pathogenic	-1.205	Destabilizing	0.807	D	0.475	neutral	None	None	None	None	N
I/D	0.8109	likely_pathogenic	0.9163	pathogenic	-2.002	Highly Destabilizing	0.525	D	0.582	neutral	None	None	None	None	N
I/E	0.6803	likely_pathogenic	0.8217	pathogenic	-1.862	Destabilizing	0.45	N	0.573	neutral	None	None	None	None	N
I/F	0.1331	likely_benign	0.1886	benign	-1.325	Destabilizing	0.076	N	0.443	neutral	N	0.509245222	None	None	N
I/G	0.7306	likely_pathogenic	0.8579	pathogenic	-2.587	Highly Destabilizing	0.525	D	0.571	neutral	None	None	None	None	N
I/H	0.5593	ambiguous	0.7038	pathogenic	-1.966	Destabilizing	0.841	D	0.595	neutral	None	None	None	None	N
I/K	0.4404	ambiguous	0.5923	pathogenic	-1.458	Destabilizing	0.016	N	0.574	neutral	None	None	None	None	N
I/L	0.0949	likely_benign	0.1075	benign	-0.819	Destabilizing	None	N	0.098	neutral	D	0.522034474	None	None	N
I/M	0.0846	likely_benign	0.094	benign	-0.609	Destabilizing	0.001	N	0.355	neutral	N	0.521554471	None	None	N
I/N	0.3551	ambiguous	0.5344	ambiguous	-1.516	Destabilizing	0.455	N	0.589	neutral	D	0.529123904	None	None	N
I/P	0.8485	likely_pathogenic	0.9262	pathogenic	-1.228	Destabilizing	0.525	D	0.588	neutral	None	None	None	None	N
I/Q	0.5007	ambiguous	0.6481	pathogenic	-1.516	Destabilizing	0.315	N	0.589	neutral	None	None	None	None	N
I/R	0.3858	ambiguous	0.5391	ambiguous	-1.067	Destabilizing	0.306	N	0.589	neutral	None	None	None	None	N
I/S	0.4571	ambiguous	0.6413	pathogenic	-2.191	Highly Destabilizing	0.292	N	0.519	neutral	N	0.500713301	None	None	N
I/T	0.4751	ambiguous	0.6514	pathogenic	-1.918	Destabilizing	0.017	N	0.448	neutral	D	0.536062564	None	None	N
I/V	0.1098	likely_benign	0.1417	benign	-1.228	Destabilizing	None	N	0.143	neutral	D	0.529688378	None	None	N
I/W	0.6908	likely_pathogenic	0.7918	pathogenic	-1.627	Destabilizing	0.95	D	0.641	neutral	None	None	None	None	N
I/Y	0.3793	ambiguous	0.4858	ambiguous	-1.327	Destabilizing	0.049	N	0.484	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.