TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33070	99433;99434;99435	chr2:178538621;178538620;178538619	chr2:179403348;179403347;179403346
N2AB	31429	94510;94511;94512	chr2:178538621;178538620;178538619	chr2:179403348;179403347;179403346
N2A	30502	91729;91730;91731	chr2:178538621;178538620;178538619	chr2:179403348;179403347;179403346
N2B	24005	72238;72239;72240	chr2:178538621;178538620;178538619	chr2:179403348;179403347;179403346
Novex-1	24130	72613;72614;72615	chr2:178538621;178538620;178538619	chr2:179403348;179403347;179403346
Novex-2	24197	72814;72815;72816	chr2:178538621;178538620;178538619	chr2:179403348;179403347;179403346
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-129
• Domain position: 73
• Structural Position: 105
• Q(SASA): 0.1799
• 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
E/Q	rs1263382518	-0.895	1.0	N	0.691	0.354	0.304760801415	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	5.57E-05	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
E/A	0.6875	likely_pathogenic	0.7225	pathogenic	-1.279	Destabilizing	0.999	D	0.655	neutral	N	0.485753738	None	None	N
E/C	0.9777	likely_pathogenic	0.979	pathogenic	-0.573	Destabilizing	1.0	D	0.748	deleterious	None	None	None	None	N
E/D	0.589	likely_pathogenic	0.6138	pathogenic	-1.583	Destabilizing	0.999	D	0.59	neutral	N	0.495566334	None	None	N
E/F	0.9795	likely_pathogenic	0.981	pathogenic	-0.955	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
E/G	0.8428	likely_pathogenic	0.8555	pathogenic	-1.714	Destabilizing	1.0	D	0.668	neutral	N	0.512442821	None	None	N
E/H	0.9347	likely_pathogenic	0.938	pathogenic	-0.895	Destabilizing	1.0	D	0.661	neutral	None	None	None	None	N
E/I	0.8373	likely_pathogenic	0.8632	pathogenic	-0.038	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
E/K	0.8597	likely_pathogenic	0.8744	pathogenic	-0.931	Destabilizing	0.999	D	0.626	neutral	N	0.469673718	None	None	N
E/L	0.9155	likely_pathogenic	0.9251	pathogenic	-0.038	Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	N
E/M	0.8976	likely_pathogenic	0.9099	pathogenic	0.657	Stabilizing	1.0	D	0.701	prob.neutral	None	None	None	None	N
E/N	0.8735	likely_pathogenic	0.8927	pathogenic	-1.355	Destabilizing	1.0	D	0.7	prob.neutral	None	None	None	None	N
E/P	0.9986	likely_pathogenic	0.9986	pathogenic	-0.435	Destabilizing	1.0	D	0.691	prob.neutral	None	None	None	None	N
E/Q	0.5024	ambiguous	0.4928	ambiguous	-1.044	Destabilizing	1.0	D	0.691	prob.neutral	N	0.51326777	None	None	N
E/R	0.8954	likely_pathogenic	0.8999	pathogenic	-0.862	Destabilizing	1.0	D	0.699	prob.neutral	None	None	None	None	N
E/S	0.7093	likely_pathogenic	0.7438	pathogenic	-2.005	Highly Destabilizing	0.999	D	0.664	neutral	None	None	None	None	N
E/T	0.7248	likely_pathogenic	0.7677	pathogenic	-1.573	Destabilizing	1.0	D	0.685	prob.neutral	None	None	None	None	N
E/V	0.7257	likely_pathogenic	0.7581	pathogenic	-0.435	Destabilizing	1.0	D	0.659	neutral	N	0.518654947	None	None	N
E/W	0.9953	likely_pathogenic	0.9954	pathogenic	-0.951	Destabilizing	1.0	D	0.749	deleterious	None	None	None	None	N
E/Y	0.9667	likely_pathogenic	0.9692	pathogenic	-0.69	Destabilizing	1.0	D	0.708	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.