TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15790	47593;47594;47595	chr2:178617983;178617982;178617981	chr2:179482710;179482709;179482708
N2AB	14149	42670;42671;42672	chr2:178617983;178617982;178617981	chr2:179482710;179482709;179482708
N2A	13222	39889;39890;39891	chr2:178617983;178617982;178617981	chr2:179482710;179482709;179482708
N2B	6725	20398;20399;20400	chr2:178617983;178617982;178617981	chr2:179482710;179482709;179482708
Novex-1	6850	20773;20774;20775	chr2:178617983;178617982;178617981	chr2:179482710;179482709;179482708
Novex-2	6917	20974;20975;20976	chr2:178617983;178617982;178617981	chr2:179482710;179482709;179482708
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: Fn3-2
• Domain position: 33
• Structural Position: 35
• Q(SASA): 0.1279
• Predicted PPI site: I

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	0.864	D	0.731	0.429	0.445410361449	gnomAD-4.0.0	1.59351E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.86259E-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	0.9803	likely_pathogenic	0.9728	pathogenic	-2.339	Highly Destabilizing	0.547	D	0.674	neutral	None	None	None	None	I
I/C	0.9895	likely_pathogenic	0.982	pathogenic	-1.504	Destabilizing	0.985	D	0.745	deleterious	None	None	None	None	I
I/D	0.9977	likely_pathogenic	0.9976	pathogenic	-2.426	Highly Destabilizing	0.981	D	0.826	deleterious	None	None	None	None	I
I/E	0.9923	likely_pathogenic	0.9925	pathogenic	-2.373	Highly Destabilizing	0.945	D	0.823	deleterious	None	None	None	None	I
I/F	0.8853	likely_pathogenic	0.8682	pathogenic	-1.689	Destabilizing	0.864	D	0.731	prob.delet.	D	0.662215887	None	None	I
I/G	0.9955	likely_pathogenic	0.9938	pathogenic	-2.734	Highly Destabilizing	0.945	D	0.817	deleterious	None	None	None	None	I
I/H	0.9963	likely_pathogenic	0.9956	pathogenic	-1.995	Destabilizing	0.995	D	0.811	deleterious	None	None	None	None	I
I/K	0.9845	likely_pathogenic	0.9832	pathogenic	-1.736	Destabilizing	0.945	D	0.824	deleterious	None	None	None	None	I
I/L	0.5695	likely_pathogenic	0.481	ambiguous	-1.269	Destabilizing	0.141	N	0.5	neutral	D	0.56018065	None	None	I
I/M	0.5095	ambiguous	0.4817	ambiguous	-0.921	Destabilizing	0.864	D	0.701	prob.neutral	D	0.719833852	None	None	I
I/N	0.959	likely_pathogenic	0.9557	pathogenic	-1.662	Destabilizing	0.975	D	0.843	deleterious	D	0.721908328	None	None	I
I/P	0.9688	likely_pathogenic	0.9633	pathogenic	-1.6	Destabilizing	0.981	D	0.837	deleterious	None	None	None	None	I
I/Q	0.9903	likely_pathogenic	0.9903	pathogenic	-1.823	Destabilizing	0.981	D	0.846	deleterious	None	None	None	None	I
I/R	0.9848	likely_pathogenic	0.9833	pathogenic	-1.09	Destabilizing	0.945	D	0.847	deleterious	None	None	None	None	I
I/S	0.9843	likely_pathogenic	0.9811	pathogenic	-2.267	Highly Destabilizing	0.864	D	0.778	deleterious	D	0.741353177	None	None	I
I/T	0.9702	likely_pathogenic	0.9538	pathogenic	-2.098	Highly Destabilizing	0.645	D	0.796	deleterious	D	0.682447528	None	None	I
I/V	0.2142	likely_benign	0.1469	benign	-1.6	Destabilizing	0.002	N	0.287	neutral	N	0.488978343	None	None	I
I/W	0.9971	likely_pathogenic	0.9965	pathogenic	-1.878	Destabilizing	0.995	D	0.77	deleterious	None	None	None	None	I
I/Y	0.9828	likely_pathogenic	0.9817	pathogenic	-1.675	Destabilizing	0.945	D	0.782	deleterious	None	None	None	None	I

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.