TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26490	79693;79694;79695	chr2:178566664;178566663;178566662	chr2:179431391;179431390;179431389
N2AB	24849	74770;74771;74772	chr2:178566664;178566663;178566662	chr2:179431391;179431390;179431389
N2A	23922	71989;71990;71991	chr2:178566664;178566663;178566662	chr2:179431391;179431390;179431389
N2B	17425	52498;52499;52500	chr2:178566664;178566663;178566662	chr2:179431391;179431390;179431389
Novex-1	17550	52873;52874;52875	chr2:178566664;178566663;178566662	chr2:179431391;179431390;179431389
Novex-2	17617	53074;53075;53076	chr2:178566664;178566663;178566662	chr2:179431391;179431390;179431389
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Fn3-81
• Domain position: 4
• Structural Position: 4
• Q(SASA): 0.2467
• 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
P/L	rs746317804	-0.761	0.549	D	0.795	0.282	None	gnomAD-2.1.1	8.06E-06	None	None	None	None	I	None	1.29282E-04	0	None	0	0	None	0	None	0	0	0
P/L	rs746317804	-0.761	0.549	D	0.795	0.282	None	gnomAD-3.1.2	1.97E-05	None	None	None	None	I	None	7.24E-05	0	0	0	0	None	0	0	0	0	0
P/L	rs746317804	-0.761	0.549	D	0.795	0.282	None	gnomAD-4.0.0	7.69371E-06	None	None	None	None	I	None	6.76979E-05	0	None	0	0	None	0	0	0	2.68039E-05	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
P/A	0.1005	likely_benign	0.1042	benign	-1.352	Destabilizing	0.201	N	0.577	neutral	N	0.499524895	None	None	I
P/C	0.5336	ambiguous	0.5094	ambiguous	-1.011	Destabilizing	0.005	N	0.543	neutral	None	None	None	None	I
P/D	0.8844	likely_pathogenic	0.8962	pathogenic	-1.621	Destabilizing	0.617	D	0.727	prob.delet.	None	None	None	None	I
P/E	0.6009	likely_pathogenic	0.6526	pathogenic	-1.676	Destabilizing	0.447	N	0.705	prob.neutral	None	None	None	None	I
P/F	0.6524	likely_pathogenic	0.6375	pathogenic	-1.345	Destabilizing	0.972	D	0.845	deleterious	None	None	None	None	I
P/G	0.5409	ambiguous	0.5315	ambiguous	-1.595	Destabilizing	0.617	D	0.767	deleterious	None	None	None	None	I
P/H	0.4559	ambiguous	0.4682	ambiguous	-1.111	Destabilizing	0.92	D	0.842	deleterious	None	None	None	None	I
P/I	0.4356	ambiguous	0.4494	ambiguous	-0.798	Destabilizing	0.92	D	0.821	deleterious	None	None	None	None	I
P/K	0.5645	likely_pathogenic	0.6237	pathogenic	-0.999	Destabilizing	0.447	N	0.744	deleterious	None	None	None	None	I
P/L	0.2234	likely_benign	0.2204	benign	-0.798	Destabilizing	0.549	D	0.795	deleterious	D	0.522660264	None	None	I
P/M	0.3967	ambiguous	0.4	ambiguous	-0.562	Destabilizing	0.92	D	0.842	deleterious	None	None	None	None	I
P/N	0.6661	likely_pathogenic	0.6746	pathogenic	-0.795	Destabilizing	0.617	D	0.811	deleterious	None	None	None	None	I
P/Q	0.3028	likely_benign	0.3419	ambiguous	-1.104	Destabilizing	0.016	N	0.437	neutral	N	0.491425277	None	None	I
P/R	0.4302	ambiguous	0.4864	ambiguous	-0.423	Destabilizing	0.681	D	0.812	deleterious	N	0.505263571	None	None	I
P/S	0.2464	likely_benign	0.2452	benign	-1.216	Destabilizing	0.045	N	0.45	neutral	N	0.481790492	None	None	I
P/T	0.2637	likely_benign	0.2623	benign	-1.178	Destabilizing	0.379	N	0.74	deleterious	N	0.517380345	None	None	I
P/V	0.32	likely_benign	0.3312	benign	-0.949	Destabilizing	0.617	D	0.779	deleterious	None	None	None	None	I
P/W	0.8792	likely_pathogenic	0.865	pathogenic	-1.451	Destabilizing	0.992	D	0.832	deleterious	None	None	None	None	I
P/Y	0.7043	likely_pathogenic	0.6965	pathogenic	-1.15	Destabilizing	0.92	D	0.844	deleterious	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.