TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27857	83794;83795;83796	chr2:178562563;178562562;178562561	chr2:179427290;179427289;179427288
N2AB	26216	78871;78872;78873	chr2:178562563;178562562;178562561	chr2:179427290;179427289;179427288
N2A	25289	76090;76091;76092	chr2:178562563;178562562;178562561	chr2:179427290;179427289;179427288
N2B	18792	56599;56600;56601	chr2:178562563;178562562;178562561	chr2:179427290;179427289;179427288
Novex-1	18917	56974;56975;56976	chr2:178562563;178562562;178562561	chr2:179427290;179427289;179427288
Novex-2	18984	57175;57176;57177	chr2:178562563;178562562;178562561	chr2:179427290;179427289;179427288
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCC
• RefSeq wild type template codon: GGG
• Domain: Fn3-90
• Domain position: 92
• Structural Position: 126
• Q(SASA): 0.2615
• 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
P/A	None	None	0.002	N	0.229	0.092	0.1749357433	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
P/L	None	None	0.651	N	0.671	0.317	0.480423546575	gnomAD-4.0.0	6.85636E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.00383E-07	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
P/A	0.068	likely_benign	0.0645	benign	-1.106	Destabilizing	0.002	N	0.229	neutral	N	0.445746338	None	None	N
P/C	0.5472	ambiguous	0.5209	ambiguous	-0.717	Destabilizing	0.995	D	0.717	prob.delet.	None	None	None	None	N
P/D	0.8532	likely_pathogenic	0.8391	pathogenic	-0.452	Destabilizing	0.712	D	0.556	neutral	None	None	None	None	N
P/E	0.6509	likely_pathogenic	0.6181	pathogenic	-0.485	Destabilizing	0.553	D	0.537	neutral	None	None	None	None	N
P/F	0.7317	likely_pathogenic	0.7133	pathogenic	-0.915	Destabilizing	0.982	D	0.719	prob.delet.	None	None	None	None	N
P/G	0.3763	ambiguous	0.3374	benign	-1.375	Destabilizing	0.553	D	0.602	neutral	None	None	None	None	N
P/H	0.5288	ambiguous	0.5081	ambiguous	-0.841	Destabilizing	0.98	D	0.633	neutral	N	0.480693493	None	None	N
P/I	0.4824	ambiguous	0.4749	ambiguous	-0.495	Destabilizing	0.897	D	0.731	deleterious	None	None	None	None	N
P/K	0.7273	likely_pathogenic	0.7149	pathogenic	-0.747	Destabilizing	0.553	D	0.558	neutral	None	None	None	None	N
P/L	0.2533	likely_benign	0.2526	benign	-0.495	Destabilizing	0.651	D	0.671	prob.neutral	N	0.472082211	None	None	N
P/M	0.4083	ambiguous	0.3888	ambiguous	-0.38	Destabilizing	0.982	D	0.635	neutral	None	None	None	None	N
P/N	0.6211	likely_pathogenic	0.5864	pathogenic	-0.496	Destabilizing	0.946	D	0.669	prob.neutral	None	None	None	None	N
P/Q	0.4258	ambiguous	0.3894	ambiguous	-0.676	Destabilizing	0.088	N	0.339	neutral	None	None	None	None	N
P/R	0.5902	likely_pathogenic	0.584	pathogenic	-0.262	Destabilizing	0.868	D	0.685	prob.delet.	N	0.503317198	None	None	N
P/S	0.1921	likely_benign	0.1763	benign	-1.053	Destabilizing	0.483	N	0.545	neutral	N	0.477282753	None	None	N
P/T	0.18	likely_benign	0.1718	benign	-0.973	Destabilizing	0.651	D	0.521	neutral	N	0.477197546	None	None	N
P/V	0.3105	likely_benign	0.2986	benign	-0.662	Destabilizing	0.553	D	0.633	neutral	None	None	None	None	N
P/W	0.8771	likely_pathogenic	0.8661	pathogenic	-1.038	Destabilizing	0.995	D	0.729	deleterious	None	None	None	None	N
P/Y	0.7199	likely_pathogenic	0.7144	pathogenic	-0.737	Destabilizing	0.982	D	0.719	prob.delet.	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.