TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32937	99034;99035;99036	chr2:178539126;178539125;178539124	chr2:179403853;179403852;179403851
N2AB	31296	94111;94112;94113	chr2:178539126;178539125;178539124	chr2:179403853;179403852;179403851
N2A	30369	91330;91331;91332	chr2:178539126;178539125;178539124	chr2:179403853;179403852;179403851
N2B	23872	71839;71840;71841	chr2:178539126;178539125;178539124	chr2:179403853;179403852;179403851
Novex-1	23997	72214;72215;72216	chr2:178539126;178539125;178539124	chr2:179403853;179403852;179403851
Novex-2	24064	72415;72416;72417	chr2:178539126;178539125;178539124	chr2:179403853;179403852;179403851
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Fn3-128
• Domain position: 42
• Structural Position: 43
• Q(SASA): 0.1647
• 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
K/E	rs200544701	-0.841	0.722	N	0.512	0.167	None	gnomAD-2.1.1	1.96287E-04	None	None	None	None	N	None	0	5.09251E-04	None	2.90135E-03	0	None	6.54E-05	None	0	1.56E-05	4.20994E-04
K/E	rs200544701	-0.841	0.722	N	0.512	0.167	None	gnomAD-3.1.2	1.05169E-04	None	None	None	None	N	None	0	2.62089E-04	0	2.59366E-03	0	None	0	0	4.41E-05	0	0
K/E	rs200544701	-0.841	0.722	N	0.512	0.167	None	gnomAD-4.0.0	9.17171E-05	None	None	None	None	N	None	1.33501E-05	4.66838E-04	None	2.80424E-03	0	None	0	0	2.11908E-05	2.19573E-05	1.44106E-04

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
K/A	0.9448	likely_pathogenic	0.9115	pathogenic	-1.325	Destabilizing	0.775	D	0.602	neutral	None	None	None	None	N
K/C	0.8814	likely_pathogenic	0.8044	pathogenic	-1.514	Destabilizing	0.996	D	0.803	deleterious	None	None	None	None	N
K/D	0.9949	likely_pathogenic	0.9929	pathogenic	-1.867	Destabilizing	0.923	D	0.681	prob.neutral	None	None	None	None	N
K/E	0.8538	likely_pathogenic	0.7995	pathogenic	-1.62	Destabilizing	0.722	D	0.512	neutral	N	0.479539199	None	None	N
K/F	0.9775	likely_pathogenic	0.9618	pathogenic	-0.735	Destabilizing	0.987	D	0.797	deleterious	None	None	None	None	N
K/G	0.963	likely_pathogenic	0.9489	pathogenic	-1.748	Destabilizing	0.775	D	0.672	neutral	None	None	None	None	N
K/H	0.7526	likely_pathogenic	0.7025	pathogenic	-2.051	Highly Destabilizing	0.961	D	0.731	prob.delet.	None	None	None	None	N
K/I	0.9059	likely_pathogenic	0.8414	pathogenic	-0.147	Destabilizing	0.949	D	0.803	deleterious	D	0.52429284	None	None	N
K/L	0.802	likely_pathogenic	0.6972	pathogenic	-0.147	Destabilizing	0.775	D	0.672	neutral	None	None	None	None	N
K/M	0.6551	likely_pathogenic	0.5371	ambiguous	-0.523	Destabilizing	0.996	D	0.714	prob.delet.	None	None	None	None	N
K/N	0.9703	likely_pathogenic	0.9592	pathogenic	-1.686	Destabilizing	0.722	D	0.519	neutral	N	0.516750792	None	None	N
K/P	0.9985	likely_pathogenic	0.998	pathogenic	-0.518	Destabilizing	0.987	D	0.721	prob.delet.	None	None	None	None	N
K/Q	0.3847	ambiguous	0.2912	benign	-1.403	Destabilizing	0.722	D	0.527	neutral	N	0.429283736	None	None	N
K/R	0.0873	likely_benign	0.0823	benign	-1.234	Destabilizing	0.003	N	0.125	neutral	N	0.385935604	None	None	N
K/S	0.9728	likely_pathogenic	0.9604	pathogenic	-2.135	Highly Destabilizing	0.775	D	0.469	neutral	None	None	None	None	N
K/T	0.9021	likely_pathogenic	0.87	pathogenic	-1.665	Destabilizing	0.722	D	0.629	neutral	N	0.51038218	None	None	N
K/V	0.8843	likely_pathogenic	0.821	pathogenic	-0.518	Destabilizing	0.961	D	0.707	prob.neutral	None	None	None	None	N
K/W	0.9579	likely_pathogenic	0.9395	pathogenic	-0.903	Destabilizing	0.996	D	0.773	deleterious	None	None	None	None	N
K/Y	0.9289	likely_pathogenic	0.8962	pathogenic	-0.499	Destabilizing	0.987	D	0.785	deleterious	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.