TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32606	98041;98042;98043	chr2:178540350;178540349;178540348	chr2:179405077;179405076;179405075
N2AB	30965	93118;93119;93120	chr2:178540350;178540349;178540348	chr2:179405077;179405076;179405075
N2A	30038	90337;90338;90339	chr2:178540350;178540349;178540348	chr2:179405077;179405076;179405075
N2B	23541	70846;70847;70848	chr2:178540350;178540349;178540348	chr2:179405077;179405076;179405075
Novex-1	23666	71221;71222;71223	chr2:178540350;178540349;178540348	chr2:179405077;179405076;179405075
Novex-2	23733	71422;71423;71424	chr2:178540350;178540349;178540348	chr2:179405077;179405076;179405075
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAC
• RefSeq wild type template codon: TTG
• Domain: Fn3-126
• Domain position: 7
• Structural Position: 7
• Q(SASA): 0.5934
• 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
N/S	None	None	0.684	N	0.375	0.295	0.159798565429	gnomAD-4.0.0	1.59441E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86497E-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
N/A	0.3921	ambiguous	0.379	ambiguous	-0.366	Destabilizing	0.742	D	0.354	neutral	None	None	None	None	N
N/C	0.3259	likely_benign	0.3276	benign	0.312	Stabilizing	0.996	D	0.478	neutral	None	None	None	None	N
N/D	0.249	likely_benign	0.2396	benign	-0.004	Destabilizing	0.684	D	0.381	neutral	N	0.50545915	None	None	N
N/E	0.4905	ambiguous	0.4639	ambiguous	-0.034	Destabilizing	0.59	D	0.326	neutral	None	None	None	None	N
N/F	0.4942	ambiguous	0.4895	ambiguous	-0.672	Destabilizing	0.91	D	0.443	neutral	None	None	None	None	N
N/G	0.5624	ambiguous	0.5481	ambiguous	-0.554	Destabilizing	0.854	D	0.335	neutral	None	None	None	None	N
N/H	0.1476	likely_benign	0.1582	benign	-0.553	Destabilizing	0.939	D	0.423	neutral	N	0.483759637	None	None	N
N/I	0.2766	likely_benign	0.2742	benign	0.043	Stabilizing	0.015	N	0.322	neutral	N	0.503167338	None	None	N
N/K	0.4343	ambiguous	0.4444	ambiguous	0.054	Stabilizing	0.028	N	0.216	neutral	N	0.519505883	None	None	N
N/L	0.3115	likely_benign	0.3072	benign	0.043	Stabilizing	0.331	N	0.397	neutral	None	None	None	None	N
N/M	0.3612	ambiguous	0.3635	ambiguous	0.416	Stabilizing	0.91	D	0.419	neutral	None	None	None	None	N
N/P	0.8803	likely_pathogenic	0.8481	pathogenic	-0.066	Destabilizing	0.984	D	0.448	neutral	None	None	None	None	N
N/Q	0.3939	ambiguous	0.3956	ambiguous	-0.447	Destabilizing	0.101	N	0.146	neutral	None	None	None	None	N
N/R	0.4872	ambiguous	0.5008	ambiguous	0.138	Stabilizing	0.59	D	0.355	neutral	None	None	None	None	N
N/S	0.1947	likely_benign	0.1899	benign	-0.204	Destabilizing	0.684	D	0.375	neutral	N	0.477074139	None	None	N
N/T	0.2701	likely_benign	0.2629	benign	-0.089	Destabilizing	0.684	D	0.316	neutral	N	0.477821381	None	None	N
N/V	0.3022	likely_benign	0.289	benign	-0.066	Destabilizing	0.331	N	0.398	neutral	None	None	None	None	N
N/W	0.794	likely_pathogenic	0.8044	pathogenic	-0.622	Destabilizing	0.996	D	0.615	neutral	None	None	None	None	N
N/Y	0.1346	likely_benign	0.1414	benign	-0.37	Destabilizing	0.939	D	0.449	neutral	D	0.533388367	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.