TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6088	18487;18488;18489	chr2:178730138;178730137;178730136	chr2:179594865;179594864;179594863
N2AB	5771	17536;17537;17538	chr2:178730138;178730137;178730136	chr2:179594865;179594864;179594863
N2A	4844	14755;14756;14757	chr2:178730138;178730137;178730136	chr2:179594865;179594864;179594863
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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: Ig-44
• Domain position: 77
• Structural Position: 161
• Q(SASA): 0.162
• 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/K	rs748182054	-0.088	1.0	D	0.744	0.515	0.227260227426	gnomAD-2.1.1	3.19E-05	None	None	None	None	N	None	0	0	None	3.44828E-03	0	None	0	None	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	0.9888	likely_pathogenic	0.9847	pathogenic	-0.184	Destabilizing	1.0	D	0.763	deleterious	None	None	None	None	N
N/C	0.9585	likely_pathogenic	0.9378	pathogenic	0.137	Stabilizing	1.0	D	0.711	prob.delet.	None	None	None	None	N
N/D	0.9369	likely_pathogenic	0.9257	pathogenic	-1.637	Destabilizing	0.999	D	0.611	neutral	N	0.515721277	None	None	N
N/E	0.9968	likely_pathogenic	0.9963	pathogenic	-1.58	Destabilizing	0.999	D	0.722	prob.delet.	None	None	None	None	N
N/F	0.9991	likely_pathogenic	0.9987	pathogenic	-0.422	Destabilizing	1.0	D	0.752	deleterious	None	None	None	None	N
N/G	0.9566	likely_pathogenic	0.9528	pathogenic	-0.445	Destabilizing	0.999	D	0.556	neutral	None	None	None	None	N
N/H	0.9544	likely_pathogenic	0.9473	pathogenic	-0.533	Destabilizing	1.0	D	0.741	deleterious	D	0.531965881	None	None	N
N/I	0.9935	likely_pathogenic	0.9891	pathogenic	0.441	Stabilizing	1.0	D	0.721	prob.delet.	D	0.54374026	None	None	N
N/K	0.9968	likely_pathogenic	0.9962	pathogenic	0.004	Stabilizing	1.0	D	0.744	deleterious	D	0.542979792	None	None	N
N/L	0.98	likely_pathogenic	0.9719	pathogenic	0.441	Stabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	N
N/M	0.9915	likely_pathogenic	0.9876	pathogenic	0.983	Stabilizing	1.0	D	0.742	deleterious	None	None	None	None	N
N/P	0.9942	likely_pathogenic	0.9938	pathogenic	0.262	Stabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	N
N/Q	0.9957	likely_pathogenic	0.9953	pathogenic	-0.945	Destabilizing	1.0	D	0.754	deleterious	None	None	None	None	N
N/R	0.994	likely_pathogenic	0.9936	pathogenic	0.111	Stabilizing	1.0	D	0.769	deleterious	None	None	None	None	N
N/S	0.5362	ambiguous	0.4972	ambiguous	-0.508	Destabilizing	0.999	D	0.575	neutral	N	0.489525946	None	None	N
N/T	0.8997	likely_pathogenic	0.861	pathogenic	-0.311	Destabilizing	0.999	D	0.711	prob.delet.	N	0.515974767	None	None	N
N/V	0.9891	likely_pathogenic	0.9827	pathogenic	0.262	Stabilizing	1.0	D	0.734	prob.delet.	None	None	None	None	N
N/W	0.9993	likely_pathogenic	0.9992	pathogenic	-0.402	Destabilizing	1.0	D	0.709	prob.delet.	None	None	None	None	N
N/Y	0.9888	likely_pathogenic	0.9853	pathogenic	0.002	Stabilizing	1.0	D	0.745	deleterious	D	0.543486771	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.