TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25190	75793;75794;75795	chr2:178570564;178570563;178570562	chr2:179435291;179435290;179435289
N2AB	23549	70870;70871;70872	chr2:178570564;178570563;178570562	chr2:179435291;179435290;179435289
N2A	22622	68089;68090;68091	chr2:178570564;178570563;178570562	chr2:179435291;179435290;179435289
N2B	16125	48598;48599;48600	chr2:178570564;178570563;178570562	chr2:179435291;179435290;179435289
Novex-1	16250	48973;48974;48975	chr2:178570564;178570563;178570562	chr2:179435291;179435290;179435289
Novex-2	16317	49174;49175;49176	chr2:178570564;178570563;178570562	chr2:179435291;179435290;179435289
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Ig-134
• Domain position: 80
• Structural Position: 163
• Q(SASA): 0.3916
• 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
A/E	rs1707808467	None	0.998	N	0.538	0.528	0.543165868402	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
A/E	rs1707808467	None	0.998	N	0.538	0.528	0.543165868402	gnomAD-4.0.0	6.57877E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.47115E-05	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
A/C	0.6261	likely_pathogenic	0.6235	pathogenic	-0.91	Destabilizing	1.0	D	0.561	neutral	None	None	None	None	I
A/D	0.9027	likely_pathogenic	0.9289	pathogenic	-0.576	Destabilizing	0.996	D	0.629	neutral	None	None	None	None	I
A/E	0.8732	likely_pathogenic	0.9064	pathogenic	-0.724	Destabilizing	0.998	D	0.538	neutral	N	0.501104921	None	None	I
A/F	0.644	likely_pathogenic	0.6547	pathogenic	-0.972	Destabilizing	0.999	D	0.707	prob.neutral	None	None	None	None	I
A/G	0.1355	likely_benign	0.1482	benign	-0.291	Destabilizing	0.011	N	0.31	neutral	N	0.49838961	None	None	I
A/H	0.8849	likely_pathogenic	0.8993	pathogenic	-0.266	Destabilizing	1.0	D	0.723	prob.delet.	None	None	None	None	I
A/I	0.7007	likely_pathogenic	0.7193	pathogenic	-0.487	Destabilizing	0.999	D	0.579	neutral	None	None	None	None	I
A/K	0.9398	likely_pathogenic	0.9604	pathogenic	-0.588	Destabilizing	0.996	D	0.539	neutral	None	None	None	None	I
A/L	0.5214	ambiguous	0.546	ambiguous	-0.487	Destabilizing	0.985	D	0.528	neutral	None	None	None	None	I
A/M	0.6091	likely_pathogenic	0.6177	pathogenic	-0.625	Destabilizing	1.0	D	0.627	neutral	None	None	None	None	I
A/N	0.7996	likely_pathogenic	0.825	pathogenic	-0.326	Destabilizing	0.996	D	0.658	neutral	None	None	None	None	I
A/P	0.9224	likely_pathogenic	0.9444	pathogenic	-0.399	Destabilizing	0.998	D	0.579	neutral	D	0.541200998	None	None	I
A/Q	0.8452	likely_pathogenic	0.8716	pathogenic	-0.582	Destabilizing	0.999	D	0.588	neutral	None	None	None	None	I
A/R	0.8737	likely_pathogenic	0.9097	pathogenic	-0.158	Destabilizing	0.999	D	0.58	neutral	None	None	None	None	I
A/S	0.1705	likely_benign	0.1701	benign	-0.508	Destabilizing	0.961	D	0.522	neutral	N	0.521746472	None	None	I
A/T	0.3218	likely_benign	0.3392	benign	-0.585	Destabilizing	0.98	D	0.493	neutral	N	0.511572172	None	None	I
A/V	0.3704	ambiguous	0.3871	ambiguous	-0.399	Destabilizing	0.993	D	0.495	neutral	N	0.517666017	None	None	I
A/W	0.9417	likely_pathogenic	0.946	pathogenic	-1.06	Destabilizing	1.0	D	0.763	deleterious	None	None	None	None	I
A/Y	0.832	likely_pathogenic	0.8506	pathogenic	-0.759	Destabilizing	0.999	D	0.709	prob.delet.	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.