TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2149	6670;6671;6672	chr2:178775419;178775418;178775417	chr2:179640146;179640145;179640144
N2AB	2149	6670;6671;6672	chr2:178775419;178775418;178775417	chr2:179640146;179640145;179640144
N2A	2149	6670;6671;6672	chr2:178775419;178775418;178775417	chr2:179640146;179640145;179640144
N2B	2103	6532;6533;6534	chr2:178775419;178775418;178775417	chr2:179640146;179640145;179640144
Novex-1	2103	6532;6533;6534	chr2:178775419;178775418;178775417	chr2:179640146;179640145;179640144
Novex-2	2103	6532;6533;6534	chr2:178775419;178775418;178775417	chr2:179640146;179640145;179640144
Novex-3	2149	6670;6671;6672	chr2:178775419;178775418;178775417	chr2:179640146;179640145;179640144

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Ig-10
• Domain position: 72
• Structural Position: 154
• Q(SASA): 0.0827
• 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/L	rs967525723	None	0.889	D	0.496	0.45	0.619116397592	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
I/L	rs967525723	None	0.889	D	0.496	0.45	0.619116397592	gnomAD-4.0.0	6.57082E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.46981E-05	0	0
I/V	rs967525723	None	0.333	N	0.373	0.252	0.586174608782	gnomAD-4.0.0	1.36821E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.7986E-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	0.9657	likely_pathogenic	0.9696	pathogenic	-2.671	Highly Destabilizing	0.992	D	0.749	deleterious	None	None	None	None	N
I/C	0.9698	likely_pathogenic	0.974	pathogenic	-1.828	Destabilizing	1.0	D	0.758	deleterious	None	None	None	None	N
I/D	0.9996	likely_pathogenic	0.9996	pathogenic	-3.525	Highly Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	N
I/E	0.9982	likely_pathogenic	0.9983	pathogenic	-3.202	Highly Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	N
I/F	0.3124	likely_benign	0.3193	benign	-1.685	Destabilizing	0.998	D	0.731	prob.delet.	N	0.48724582	None	None	N
I/G	0.9962	likely_pathogenic	0.9968	pathogenic	-3.275	Highly Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
I/H	0.9924	likely_pathogenic	0.9927	pathogenic	-3.085	Highly Destabilizing	1.0	D	0.848	deleterious	None	None	None	None	N
I/K	0.9967	likely_pathogenic	0.9968	pathogenic	-2.116	Highly Destabilizing	1.0	D	0.874	deleterious	None	None	None	None	N
I/L	0.2053	likely_benign	0.2131	benign	-0.85	Destabilizing	0.889	D	0.496	neutral	D	0.525036179	None	None	N
I/M	0.2786	likely_benign	0.2857	benign	-0.952	Destabilizing	0.998	D	0.699	prob.neutral	D	0.592007342	None	None	N
I/N	0.9894	likely_pathogenic	0.9901	pathogenic	-2.863	Highly Destabilizing	0.999	D	0.87	deleterious	D	0.591204003	None	None	N
I/P	0.9989	likely_pathogenic	0.9991	pathogenic	-1.448	Destabilizing	1.0	D	0.866	deleterious	None	None	None	None	N
I/Q	0.9953	likely_pathogenic	0.9957	pathogenic	-2.502	Highly Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	N
I/R	0.9929	likely_pathogenic	0.9931	pathogenic	-2.184	Highly Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	N
I/S	0.984	likely_pathogenic	0.9863	pathogenic	-3.375	Highly Destabilizing	0.998	D	0.834	deleterious	D	0.591204003	None	None	N
I/T	0.9573	likely_pathogenic	0.9609	pathogenic	-2.889	Highly Destabilizing	0.989	D	0.774	deleterious	D	0.592007342	None	None	N
I/V	0.0964	likely_benign	0.0951	benign	-1.448	Destabilizing	0.333	N	0.373	neutral	N	0.467379771	None	None	N
I/W	0.9752	likely_pathogenic	0.9764	pathogenic	-2.162	Highly Destabilizing	1.0	D	0.824	deleterious	None	None	None	None	N
I/Y	0.8464	likely_pathogenic	0.8493	pathogenic	-1.905	Destabilizing	1.0	D	0.765	deleterious	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.