TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24839	74740;74741;74742	chr2:178571617;178571616;178571615	chr2:179436344;179436343;179436342
N2AB	23198	69817;69818;69819	chr2:178571617;178571616;178571615	chr2:179436344;179436343;179436342
N2A	22271	67036;67037;67038	chr2:178571617;178571616;178571615	chr2:179436344;179436343;179436342
N2B	15774	47545;47546;47547	chr2:178571617;178571616;178571615	chr2:179436344;179436343;179436342
Novex-1	15899	47920;47921;47922	chr2:178571617;178571616;178571615	chr2:179436344;179436343;179436342
Novex-2	15966	48121;48122;48123	chr2:178571617;178571616;178571615	chr2:179436344;179436343;179436342
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGT
• RefSeq wild type template codon: TCA
• Domain: Fn3-68
• Domain position: 32
• Structural Position: 33
• Q(SASA): 0.2266
• 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
S/G	rs770901672	-1.227	0.815	N	0.55	0.18	0.183819452728	gnomAD-2.1.1	4.04E-06	None	None	None	None	I	None	6.48E-05	0	None	0	0	None	0	None	0	0	0
S/G	rs770901672	-1.227	0.815	N	0.55	0.18	0.183819452728	gnomAD-3.1.2	1.31E-05	None	None	None	None	I	None	4.83E-05	0	0	0	0	None	0	0	0	0	0
S/G	rs770901672	-1.227	0.815	N	0.55	0.18	0.183819452728	gnomAD-4.0.0	1.31482E-05	None	None	None	None	I	None	4.82509E-05	0	None	0	0	None	0	0	0	0	0
S/N	rs763157776	-0.557	0.931	N	0.653	0.309	0.27132560031	gnomAD-2.1.1	1.21E-05	None	None	None	None	I	None	0	8.72E-05	None	0	0	None	0	None	0	0	0
S/N	rs763157776	-0.557	0.931	N	0.653	0.309	0.27132560031	gnomAD-4.0.0	3.42212E-06	None	None	None	None	I	None	0	6.71171E-05	None	0	0	None	0	0	1.79923E-06	0	0
S/R	rs1301601226	None	0.979	N	0.631	0.37	0.246773566709	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
S/R	rs1301601226	None	0.979	N	0.631	0.37	0.246773566709	gnomAD-4.0.0	1.36382E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.7803E-05	0	1.60174E-05
S/T	rs763157776	-0.629	0.684	N	0.58	0.222	0.227260227426	gnomAD-2.1.1	3.19E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	6.48E-05	0
S/T	rs763157776	-0.629	0.684	N	0.58	0.222	0.227260227426	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
S/T	rs763157776	-0.629	0.684	N	0.58	0.222	0.227260227426	gnomAD-4.0.0	3.71941E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	5.08657E-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
S/A	0.1237	likely_benign	0.1284	benign	-0.992	Destabilizing	0.206	N	0.476	neutral	None	None	None	None	I
S/C	0.0715	likely_benign	0.0744	benign	-0.619	Destabilizing	0.003	N	0.361	neutral	N	0.426747651	None	None	I
S/D	0.9533	likely_pathogenic	0.9564	pathogenic	-0.317	Destabilizing	0.947	D	0.627	neutral	None	None	None	None	I
S/E	0.9756	likely_pathogenic	0.9773	pathogenic	-0.342	Destabilizing	0.947	D	0.626	neutral	None	None	None	None	I
S/F	0.6638	likely_pathogenic	0.6579	pathogenic	-1.344	Destabilizing	0.953	D	0.667	neutral	None	None	None	None	I
S/G	0.1872	likely_benign	0.1837	benign	-1.197	Destabilizing	0.815	D	0.55	neutral	N	0.510741966	None	None	I
S/H	0.8714	likely_pathogenic	0.8758	pathogenic	-1.663	Destabilizing	0.996	D	0.61	neutral	None	None	None	None	I
S/I	0.5104	ambiguous	0.5376	ambiguous	-0.55	Destabilizing	0.884	D	0.672	neutral	N	0.482297471	None	None	I
S/K	0.9914	likely_pathogenic	0.9922	pathogenic	-0.741	Destabilizing	0.854	D	0.629	neutral	None	None	None	None	I
S/L	0.366	ambiguous	0.3535	ambiguous	-0.55	Destabilizing	0.59	D	0.581	neutral	None	None	None	None	I
S/M	0.4771	ambiguous	0.4769	ambiguous	-0.083	Destabilizing	0.984	D	0.62	neutral	None	None	None	None	I
S/N	0.5652	likely_pathogenic	0.6035	pathogenic	-0.648	Destabilizing	0.931	D	0.653	neutral	N	0.482297471	None	None	I
S/P	0.9792	likely_pathogenic	0.9801	pathogenic	-0.667	Destabilizing	0.984	D	0.637	neutral	None	None	None	None	I
S/Q	0.9341	likely_pathogenic	0.9367	pathogenic	-0.886	Destabilizing	0.984	D	0.632	neutral	None	None	None	None	I
S/R	0.9801	likely_pathogenic	0.9814	pathogenic	-0.557	Destabilizing	0.979	D	0.631	neutral	N	0.514998566	None	None	I
S/T	0.165	likely_benign	0.1808	benign	-0.732	Destabilizing	0.684	D	0.58	neutral	N	0.507592591	None	None	I
S/V	0.4037	ambiguous	0.4383	ambiguous	-0.667	Destabilizing	0.742	D	0.615	neutral	None	None	None	None	I
S/W	0.8589	likely_pathogenic	0.8563	pathogenic	-1.245	Destabilizing	0.996	D	0.685	prob.neutral	None	None	None	None	I
S/Y	0.6783	likely_pathogenic	0.6742	pathogenic	-1.01	Destabilizing	0.984	D	0.666	neutral	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.