TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24557	73894;73895;73896	chr2:178572463;178572462;178572461	chr2:179437190;179437189;179437188
N2AB	22916	68971;68972;68973	chr2:178572463;178572462;178572461	chr2:179437190;179437189;179437188
N2A	21989	66190;66191;66192	chr2:178572463;178572462;178572461	chr2:179437190;179437189;179437188
N2B	15492	46699;46700;46701	chr2:178572463;178572462;178572461	chr2:179437190;179437189;179437188
Novex-1	15617	47074;47075;47076	chr2:178572463;178572462;178572461	chr2:179437190;179437189;179437188
Novex-2	15684	47275;47276;47277	chr2:178572463;178572462;178572461	chr2:179437190;179437189;179437188
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: Fn3-66
• Domain position: 39
• Structural Position: 41
• Q(SASA): 0.1205
• 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	rs747530483	-1.611	1.0	N	0.67	0.478	0.445107144611	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.9E-06	0
E/K	rs747530483	-1.611	1.0	N	0.67	0.478	0.445107144611	gnomAD-4.0.0	1.08029E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.18125E-05	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	0.9603	likely_pathogenic	0.9234	pathogenic	-1.972	Destabilizing	1.0	D	0.678	prob.neutral	D	0.531899748	None	None	N
E/C	0.995	likely_pathogenic	0.994	pathogenic	-1.012	Destabilizing	1.0	D	0.778	deleterious	None	None	None	None	N
E/D	0.9114	likely_pathogenic	0.8986	pathogenic	-1.683	Destabilizing	0.998	D	0.643	neutral	N	0.485411343	None	None	N
E/F	0.9989	likely_pathogenic	0.9981	pathogenic	-1.676	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
E/G	0.9736	likely_pathogenic	0.9471	pathogenic	-2.357	Highly Destabilizing	1.0	D	0.746	deleterious	D	0.538447115	None	None	N
E/H	0.9954	likely_pathogenic	0.9918	pathogenic	-1.447	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
E/I	0.9945	likely_pathogenic	0.9904	pathogenic	-0.86	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
E/K	0.9874	likely_pathogenic	0.9725	pathogenic	-1.558	Destabilizing	1.0	D	0.67	neutral	N	0.519111411	None	None	N
E/L	0.9934	likely_pathogenic	0.9866	pathogenic	-0.86	Destabilizing	1.0	D	0.772	deleterious	None	None	None	None	N
E/M	0.9895	likely_pathogenic	0.9802	pathogenic	-0.08	Destabilizing	1.0	D	0.774	deleterious	None	None	None	None	N
E/N	0.9902	likely_pathogenic	0.9832	pathogenic	-1.752	Destabilizing	1.0	D	0.806	deleterious	None	None	None	None	N
E/P	0.9999	likely_pathogenic	0.9998	pathogenic	-1.218	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
E/Q	0.739	likely_pathogenic	0.6036	pathogenic	-1.53	Destabilizing	1.0	D	0.764	deleterious	N	0.507917878	None	None	N
E/R	0.9893	likely_pathogenic	0.9797	pathogenic	-1.315	Destabilizing	1.0	D	0.8	deleterious	None	None	None	None	N
E/S	0.9597	likely_pathogenic	0.9266	pathogenic	-2.467	Highly Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	N
E/T	0.9889	likely_pathogenic	0.9768	pathogenic	-2.092	Highly Destabilizing	1.0	D	0.767	deleterious	None	None	None	None	N
E/V	0.9852	likely_pathogenic	0.9724	pathogenic	-1.218	Destabilizing	1.0	D	0.737	prob.delet.	N	0.519328901	None	None	N
E/W	0.9995	likely_pathogenic	0.9993	pathogenic	-1.601	Destabilizing	1.0	D	0.78	deleterious	None	None	None	None	N
E/Y	0.998	likely_pathogenic	0.9972	pathogenic	-1.421	Destabilizing	1.0	D	0.775	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.