TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21229	63910;63911;63912	chr2:178587624;178587623;178587622	chr2:179452351;179452350;179452349
N2AB	19588	58987;58988;58989	chr2:178587624;178587623;178587622	chr2:179452351;179452350;179452349
N2A	18661	56206;56207;56208	chr2:178587624;178587623;178587622	chr2:179452351;179452350;179452349
N2B	12164	36715;36716;36717	chr2:178587624;178587623;178587622	chr2:179452351;179452350;179452349
Novex-1	12289	37090;37091;37092	chr2:178587624;178587623;178587622	chr2:179452351;179452350;179452349
Novex-2	12356	37291;37292;37293	chr2:178587624;178587623;178587622	chr2:179452351;179452350;179452349
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCC
• RefSeq wild type template codon: CGG
• Domain: Ig-123
• Domain position: 53
• Structural Position: 136
• Q(SASA): 0.1039
• 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
A/V	rs1209410552	None	0.961	N	0.705	0.222	0.350088858571	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	6.56E-05	0	0	0	None	0	0	0	0	0
A/V	rs1209410552	None	0.961	N	0.705	0.222	0.350088858571	gnomAD-4.0.0	1.02638E-05	None	None	None	None	N	None	0	1.69727E-05	None	0	9.76276E-05	None	0	0	7.18522E-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
A/C	0.5814	likely_pathogenic	0.556	ambiguous	-0.389	Destabilizing	1.0	D	0.742	deleterious	None	None	None	None	N
A/D	0.9482	likely_pathogenic	0.9379	pathogenic	-2.097	Highly Destabilizing	0.989	D	0.749	deleterious	N	0.490995838	None	None	N
A/E	0.9146	likely_pathogenic	0.898	pathogenic	-1.811	Destabilizing	0.97	D	0.733	prob.delet.	None	None	None	None	N
A/F	0.8593	likely_pathogenic	0.8324	pathogenic	-0.309	Destabilizing	0.999	D	0.758	deleterious	None	None	None	None	N
A/G	0.3713	ambiguous	0.3537	ambiguous	-1.201	Destabilizing	0.91	D	0.69	prob.neutral	N	0.439662941	None	None	N
A/H	0.928	likely_pathogenic	0.9156	pathogenic	-1.954	Destabilizing	1.0	D	0.756	deleterious	None	None	None	None	N
A/I	0.6037	likely_pathogenic	0.5485	ambiguous	0.891	Stabilizing	0.991	D	0.752	deleterious	None	None	None	None	N
A/K	0.9707	likely_pathogenic	0.9676	pathogenic	-0.607	Destabilizing	0.97	D	0.735	prob.delet.	None	None	None	None	N
A/L	0.4751	ambiguous	0.4425	ambiguous	0.891	Stabilizing	0.97	D	0.721	prob.delet.	None	None	None	None	N
A/M	0.5581	ambiguous	0.5179	ambiguous	0.572	Stabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	N
A/N	0.8341	likely_pathogenic	0.8082	pathogenic	-1.15	Destabilizing	0.991	D	0.753	deleterious	None	None	None	None	N
A/P	0.9582	likely_pathogenic	0.9547	pathogenic	0.421	Stabilizing	0.994	D	0.75	deleterious	N	0.499711322	None	None	N
A/Q	0.8918	likely_pathogenic	0.8823	pathogenic	-0.765	Destabilizing	0.996	D	0.763	deleterious	None	None	None	None	N
A/R	0.9507	likely_pathogenic	0.9442	pathogenic	-1.101	Destabilizing	0.996	D	0.745	deleterious	None	None	None	None	N
A/S	0.2038	likely_benign	0.1875	benign	-1.496	Destabilizing	0.287	N	0.447	neutral	N	0.381729358	None	None	N
A/T	0.1753	likely_benign	0.1436	benign	-1.061	Destabilizing	0.248	N	0.573	neutral	N	0.340845528	None	None	N
A/V	0.2928	likely_benign	0.2483	benign	0.421	Stabilizing	0.961	D	0.705	prob.neutral	N	0.474716877	None	None	N
A/W	0.9789	likely_pathogenic	0.9753	pathogenic	-1.255	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	N
A/Y	0.902	likely_pathogenic	0.8885	pathogenic	-0.564	Destabilizing	0.999	D	0.762	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.