TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	34284	103075;103076;103077	chr2:178533765;178533764;178533763	chr2:179398492;179398491;179398490
N2AB	32643	98152;98153;98154	chr2:178533765;178533764;178533763	chr2:179398492;179398491;179398490
N2A	31716	95371;95372;95373	chr2:178533765;178533764;178533763	chr2:179398492;179398491;179398490
N2B	25219	75880;75881;75882	chr2:178533765;178533764;178533763	chr2:179398492;179398491;179398490
Novex-1	25344	76255;76256;76257	chr2:178533765;178533764;178533763	chr2:179398492;179398491;179398490
Novex-2	25411	76456;76457;76458	chr2:178533765;178533764;178533763	chr2:179398492;179398491;179398490
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: H
• RefSeq wild type transcript codon: CAC
• RefSeq wild type template codon: GTG
• Domain: Ig-161
• Domain position: 27
• Structural Position: 41
• Q(SASA): 0.5411
• 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
H/R	rs879025670	None	0.811	N	0.521	0.424	None	gnomAD-4.0.0	1.59098E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85771E-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
H/A	0.8659	likely_pathogenic	0.8799	pathogenic	0.49	Stabilizing	0.919	D	0.613	neutral	None	None	None	None	I
H/C	0.6514	likely_pathogenic	0.6544	pathogenic	0.608	Stabilizing	0.999	D	0.729	prob.delet.	None	None	None	None	I
H/D	0.8201	likely_pathogenic	0.8299	pathogenic	-0.346	Destabilizing	0.896	D	0.586	neutral	N	0.452633104	None	None	I
H/E	0.8894	likely_pathogenic	0.8965	pathogenic	-0.344	Destabilizing	0.851	D	0.495	neutral	None	None	None	None	I
H/F	0.6058	likely_pathogenic	0.6558	pathogenic	0.979	Stabilizing	0.996	D	0.558	neutral	None	None	None	None	I
H/G	0.9439	likely_pathogenic	0.9531	pathogenic	0.28	Stabilizing	0.919	D	0.625	neutral	None	None	None	None	I
H/I	0.8335	likely_pathogenic	0.8489	pathogenic	1.003	Stabilizing	0.988	D	0.673	neutral	None	None	None	None	I
H/K	0.8498	likely_pathogenic	0.8797	pathogenic	0.354	Stabilizing	0.851	D	0.613	neutral	None	None	None	None	I
H/L	0.5061	ambiguous	0.5355	ambiguous	1.003	Stabilizing	0.968	D	0.591	neutral	N	0.491556851	None	None	I
H/M	0.877	likely_pathogenic	0.8902	pathogenic	0.631	Stabilizing	0.999	D	0.658	neutral	None	None	None	None	I
H/N	0.4655	ambiguous	0.5271	ambiguous	0.197	Stabilizing	0.896	D	0.557	neutral	N	0.467890558	None	None	I
H/P	0.7619	likely_pathogenic	0.6959	pathogenic	0.854	Stabilizing	0.984	D	0.659	neutral	N	0.484794184	None	None	I
H/Q	0.7689	likely_pathogenic	0.8197	pathogenic	0.256	Stabilizing	0.211	N	0.313	neutral	N	0.494903801	None	None	I
H/R	0.6474	likely_pathogenic	0.7114	pathogenic	-0.147	Destabilizing	0.811	D	0.521	neutral	N	0.490402058	None	None	I
H/S	0.7077	likely_pathogenic	0.7427	pathogenic	0.393	Stabilizing	0.919	D	0.612	neutral	None	None	None	None	I
H/T	0.8621	likely_pathogenic	0.8844	pathogenic	0.482	Stabilizing	0.976	D	0.58	neutral	None	None	None	None	I
H/V	0.8324	likely_pathogenic	0.8514	pathogenic	0.854	Stabilizing	0.988	D	0.649	neutral	None	None	None	None	I
H/W	0.7114	likely_pathogenic	0.706	pathogenic	0.839	Stabilizing	0.999	D	0.731	prob.delet.	None	None	None	None	I
H/Y	0.256	likely_benign	0.2988	benign	1.102	Stabilizing	0.982	D	0.505	neutral	N	0.474664601	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.