TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35452	106579;106580;106581	chr2:178530261;178530260;178530259	chr2:179394988;179394987;179394986
N2AB	33811	101656;101657;101658	chr2:178530261;178530260;178530259	chr2:179394988;179394987;179394986
N2A	32884	98875;98876;98877	chr2:178530261;178530260;178530259	chr2:179394988;179394987;179394986
N2B	26387	79384;79385;79386	chr2:178530261;178530260;178530259	chr2:179394988;179394987;179394986
Novex-1	26512	79759;79760;79761	chr2:178530261;178530260;178530259	chr2:179394988;179394987;179394986
Novex-2	26579	79960;79961;79962	chr2:178530261;178530260;178530259	chr2:179394988;179394987;179394986
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-166
• Domain position: 33
• Structural Position: 47
• Q(SASA): 0.395
• 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/M	None	None	0.074	N	0.526	0.03	0.292062946507	gnomAD-4.0.0	1.61619E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.46675E-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
I/A	0.1641	likely_benign	0.1535	benign	-1.276	Destabilizing	0.003	N	0.36	neutral	None	None	None	None	N
I/C	0.5789	likely_pathogenic	0.5585	ambiguous	-0.561	Destabilizing	0.177	N	0.535	neutral	None	None	None	None	N
I/D	0.3023	likely_benign	0.2866	benign	-0.67	Destabilizing	0.029	N	0.524	neutral	None	None	None	None	N
I/E	0.255	likely_benign	0.2415	benign	-0.722	Destabilizing	0.015	N	0.523	neutral	None	None	None	None	N
I/F	0.1088	likely_benign	0.0993	benign	-1.065	Destabilizing	0.022	N	0.497	neutral	N	0.492442286	None	None	N
I/G	0.3873	ambiguous	0.3682	ambiguous	-1.539	Destabilizing	0.006	N	0.481	neutral	None	None	None	None	N
I/H	0.2894	likely_benign	0.2746	benign	-0.844	Destabilizing	0.177	N	0.552	neutral	None	None	None	None	N
I/K	0.2318	likely_benign	0.2183	benign	-0.697	Destabilizing	0.015	N	0.525	neutral	None	None	None	None	N
I/L	0.0984	likely_benign	0.0936	benign	-0.659	Destabilizing	0.002	N	0.365	neutral	N	0.472163014	None	None	N
I/M	0.1009	likely_benign	0.0946	benign	-0.402	Destabilizing	0.074	N	0.526	neutral	N	0.489575339	None	None	N
I/N	0.1067	likely_benign	0.1054	benign	-0.36	Destabilizing	0.011	N	0.536	neutral	N	0.488881906	None	None	N
I/P	0.7483	likely_pathogenic	0.7706	pathogenic	-0.832	Destabilizing	0.058	N	0.546	neutral	None	None	None	None	N
I/Q	0.2458	likely_benign	0.2302	benign	-0.599	Destabilizing	0.096	N	0.596	neutral	None	None	None	None	N
I/R	0.1749	likely_benign	0.1649	benign	-0.108	Destabilizing	0.029	N	0.573	neutral	None	None	None	None	N
I/S	0.117	likely_benign	0.1119	benign	-0.9	Destabilizing	None	N	0.383	neutral	N	0.41082098	None	None	N
I/T	0.0951	likely_benign	0.0886	benign	-0.841	Destabilizing	None	N	0.299	neutral	N	0.379847499	None	None	N
I/V	0.0728	likely_benign	0.0676	benign	-0.832	Destabilizing	None	N	0.212	neutral	N	0.453595896	None	None	N
I/W	0.6339	likely_pathogenic	0.6084	pathogenic	-1.101	Destabilizing	0.712	D	0.572	neutral	None	None	None	None	N
I/Y	0.3144	likely_benign	0.3044	benign	-0.869	Destabilizing	0.177	N	0.574	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.