TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27885	83878;83879;83880	chr2:178562479;178562478;178562477	chr2:179427206;179427205;179427204
N2AB	26244	78955;78956;78957	chr2:178562479;178562478;178562477	chr2:179427206;179427205;179427204
N2A	25317	76174;76175;76176	chr2:178562479;178562478;178562477	chr2:179427206;179427205;179427204
N2B	18820	56683;56684;56685	chr2:178562479;178562478;178562477	chr2:179427206;179427205;179427204
Novex-1	18945	57058;57059;57060	chr2:178562479;178562478;178562477	chr2:179427206;179427205;179427204
Novex-2	19012	57259;57260;57261	chr2:178562479;178562478;178562477	chr2:179427206;179427205;179427204
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Fn3-91
• Domain position: 23
• Structural Position: 25
• Q(SASA): 0.4425
• 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/K	None	None	0.195	N	0.513	0.211	0.223847106136	gnomAD-4.0.0	1.59231E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85941E-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
E/A	0.3458	ambiguous	0.3412	ambiguous	-0.79	Destabilizing	0.115	N	0.623	neutral	N	0.509747462	None	None	N
E/C	0.9261	likely_pathogenic	0.9225	pathogenic	-0.484	Destabilizing	0.966	D	0.809	deleterious	None	None	None	None	N
E/D	0.1844	likely_benign	0.185	benign	-0.945	Destabilizing	None	N	0.306	neutral	N	0.510496824	None	None	N
E/F	0.9149	likely_pathogenic	0.9166	pathogenic	-0.238	Destabilizing	0.933	D	0.783	deleterious	None	None	None	None	N
E/G	0.2827	likely_benign	0.3014	benign	-1.125	Destabilizing	0.003	N	0.395	neutral	N	0.478943336	None	None	N
E/H	0.7639	likely_pathogenic	0.7669	pathogenic	-0.368	Destabilizing	0.765	D	0.603	neutral	None	None	None	None	N
E/I	0.5992	likely_pathogenic	0.5919	pathogenic	0.114	Stabilizing	0.681	D	0.787	deleterious	None	None	None	None	N
E/K	0.4188	ambiguous	0.4407	ambiguous	-0.561	Destabilizing	0.195	N	0.513	neutral	N	0.478211047	None	None	N
E/L	0.5627	ambiguous	0.5817	pathogenic	0.114	Stabilizing	0.513	D	0.72	prob.delet.	None	None	None	None	N
E/M	0.6215	likely_pathogenic	0.6371	pathogenic	0.423	Stabilizing	0.814	D	0.775	deleterious	None	None	None	None	N
E/N	0.4248	ambiguous	0.4248	ambiguous	-1.038	Destabilizing	0.065	N	0.57	neutral	None	None	None	None	N
E/P	0.8942	likely_pathogenic	0.8895	pathogenic	-0.166	Destabilizing	0.241	N	0.744	deleterious	None	None	None	None	N
E/Q	0.2336	likely_benign	0.2411	benign	-0.904	Destabilizing	0.548	D	0.569	neutral	N	0.507533876	None	None	N
E/R	0.5529	ambiguous	0.5725	pathogenic	-0.213	Destabilizing	0.005	N	0.333	neutral	None	None	None	None	N
E/S	0.3955	ambiguous	0.396	ambiguous	-1.288	Destabilizing	0.147	N	0.499	neutral	None	None	None	None	N
E/T	0.4214	ambiguous	0.4051	ambiguous	-1.013	Destabilizing	0.626	D	0.692	prob.neutral	None	None	None	None	N
E/V	0.3739	ambiguous	0.3757	ambiguous	-0.166	Destabilizing	0.533	D	0.735	prob.delet.	N	0.502456131	None	None	N
E/W	0.9643	likely_pathogenic	0.9675	pathogenic	0.015	Stabilizing	0.993	D	0.789	deleterious	None	None	None	None	N
E/Y	0.8468	likely_pathogenic	0.8532	pathogenic	-0.003	Destabilizing	0.974	D	0.788	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.