TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26689	80290;80291;80292	chr2:178566067;178566066;178566065	chr2:179430794;179430793;179430792
N2AB	25048	75367;75368;75369	chr2:178566067;178566066;178566065	chr2:179430794;179430793;179430792
N2A	24121	72586;72587;72588	chr2:178566067;178566066;178566065	chr2:179430794;179430793;179430792
N2B	17624	53095;53096;53097	chr2:178566067;178566066;178566065	chr2:179430794;179430793;179430792
Novex-1	17749	53470;53471;53472	chr2:178566067;178566066;178566065	chr2:179430794;179430793;179430792
Novex-2	17816	53671;53672;53673	chr2:178566067;178566066;178566065	chr2:179430794;179430793;179430792
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Fn3-82
• Domain position: 7
• Structural Position: 7
• Q(SASA): 0.6897
• 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
N/D	rs1289700659	0.38	0.014	N	0.247	0.174	0.136095386433	gnomAD-2.1.1	3.18E-05	None	None	None	None	I	None	1.14732E-04	0	None	0	0	None	0	None	0	0	0
N/D	rs1289700659	0.38	0.014	N	0.247	0.174	0.136095386433	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
N/D	rs1289700659	0.38	0.014	N	0.247	0.174	0.136095386433	gnomAD-4.0.0	6.57237E-06	None	None	None	None	I	None	2.41196E-05	0	None	0	0	None	0	0	0	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
N/A	0.2637	likely_benign	0.2637	benign	-0.293	Destabilizing	0.86	D	0.516	neutral	None	None	None	None	I
N/C	0.2644	likely_benign	0.2809	benign	0.286	Stabilizing	0.998	D	0.745	deleterious	None	None	None	None	I
N/D	0.1736	likely_benign	0.1672	benign	0.045	Stabilizing	0.014	N	0.247	neutral	N	0.492260567	None	None	I
N/E	0.4052	ambiguous	0.3891	ambiguous	0.019	Stabilizing	0.754	D	0.513	neutral	None	None	None	None	I
N/F	0.5202	ambiguous	0.504	ambiguous	-0.601	Destabilizing	0.993	D	0.677	prob.neutral	None	None	None	None	I
N/G	0.2713	likely_benign	0.2777	benign	-0.481	Destabilizing	0.86	D	0.496	neutral	None	None	None	None	I
N/H	0.1094	likely_benign	0.112	benign	-0.47	Destabilizing	0.97	D	0.516	neutral	N	0.49264718	None	None	I
N/I	0.3105	likely_benign	0.3043	benign	0.116	Stabilizing	0.97	D	0.688	prob.neutral	N	0.518802831	None	None	I
N/K	0.2563	likely_benign	0.2429	benign	0.027	Stabilizing	0.698	D	0.507	neutral	N	0.509808964	None	None	I
N/L	0.2921	likely_benign	0.2932	benign	0.116	Stabilizing	0.978	D	0.572	neutral	None	None	None	None	I
N/M	0.3458	ambiguous	0.3426	ambiguous	0.357	Stabilizing	0.998	D	0.662	neutral	None	None	None	None	I
N/P	0.8356	likely_pathogenic	0.8466	pathogenic	0.007	Stabilizing	0.978	D	0.663	neutral	None	None	None	None	I
N/Q	0.2826	likely_benign	0.2762	benign	-0.435	Destabilizing	0.356	N	0.257	neutral	None	None	None	None	I
N/R	0.337	likely_benign	0.3258	benign	0.083	Stabilizing	0.956	D	0.502	neutral	None	None	None	None	I
N/S	0.1301	likely_benign	0.1259	benign	-0.212	Destabilizing	0.822	D	0.529	neutral	N	0.477732476	None	None	I
N/T	0.2119	likely_benign	0.2062	benign	-0.095	Destabilizing	0.822	D	0.519	neutral	N	0.48572142	None	None	I
N/V	0.3036	likely_benign	0.3029	benign	0.007	Stabilizing	0.978	D	0.653	neutral	None	None	None	None	I
N/W	0.7978	likely_pathogenic	0.7969	pathogenic	-0.589	Destabilizing	0.998	D	0.741	deleterious	None	None	None	None	I
N/Y	0.1685	likely_benign	0.1701	benign	-0.326	Destabilizing	0.99	D	0.675	prob.neutral	D	0.530919605	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.