TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14253	42982;42983;42984	chr2:178633602;178633601;178633600	chr2:179498329;179498328;179498327
N2AB	12612	38059;38060;38061	chr2:178633602;178633601;178633600	chr2:179498329;179498328;179498327
N2A	11685	35278;35279;35280	chr2:178633602;178633601;178633600	chr2:179498329;179498328;179498327
N2B	5188	15787;15788;15789	chr2:178633602;178633601;178633600	chr2:179498329;179498328;179498327
Novex-1	5313	16162;16163;16164	chr2:178633602;178633601;178633600	chr2:179498329;179498328;179498327
Novex-2	5380	16363;16364;16365	chr2:178633602;178633601;178633600	chr2:179498329;179498328;179498327
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: Ig-93
• Domain position: 23
• Structural Position: 34
• Q(SASA): 0.3249
• 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	rs1276212237	None	0.015	D	0.296	0.244	0.265010934533	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
E/Q	rs1276212237	None	0.015	D	0.296	0.244	0.265010934533	gnomAD-4.0.0	2.56379E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	4.78806E-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	0.4374	ambiguous	0.3589	ambiguous	-1.058	Destabilizing	0.002	N	0.391	neutral	D	0.602123773	None	None	N
E/C	0.9738	likely_pathogenic	0.9727	pathogenic	-0.554	Destabilizing	0.947	D	0.723	prob.delet.	None	None	None	None	N
E/D	0.4633	ambiguous	0.4977	ambiguous	-1.211	Destabilizing	0.334	N	0.482	neutral	D	0.606297485	None	None	N
E/F	0.9446	likely_pathogenic	0.9366	pathogenic	-0.749	Destabilizing	0.826	D	0.751	deleterious	None	None	None	None	N
E/G	0.6625	likely_pathogenic	0.6104	pathogenic	-1.415	Destabilizing	0.201	N	0.659	neutral	D	0.657072294	None	None	N
E/H	0.8597	likely_pathogenic	0.8587	pathogenic	-1.062	Destabilizing	0.947	D	0.653	neutral	None	None	None	None	N
E/I	0.6755	likely_pathogenic	0.6599	pathogenic	-0.079	Destabilizing	0.7	D	0.763	deleterious	None	None	None	None	N
E/K	0.5432	ambiguous	0.4991	ambiguous	-0.759	Destabilizing	0.201	N	0.531	neutral	D	0.555706315	None	None	N
E/L	0.8177	likely_pathogenic	0.7942	pathogenic	-0.079	Destabilizing	0.539	D	0.733	prob.delet.	None	None	None	None	N
E/M	0.7801	likely_pathogenic	0.735	pathogenic	0.469	Stabilizing	0.947	D	0.731	prob.delet.	None	None	None	None	N
E/N	0.7161	likely_pathogenic	0.6969	pathogenic	-1.114	Destabilizing	0.7	D	0.631	neutral	None	None	None	None	N
E/P	0.9888	likely_pathogenic	0.9908	pathogenic	-0.385	Destabilizing	0.7	D	0.761	deleterious	None	None	None	None	N
E/Q	0.3632	ambiguous	0.3363	benign	-1.005	Destabilizing	0.015	N	0.296	neutral	D	0.554679116	None	None	N
E/R	0.6855	likely_pathogenic	0.6507	pathogenic	-0.591	Destabilizing	0.539	D	0.643	neutral	None	None	None	None	N
E/S	0.5808	likely_pathogenic	0.5134	ambiguous	-1.512	Destabilizing	0.25	N	0.526	neutral	None	None	None	None	N
E/T	0.5701	likely_pathogenic	0.5257	ambiguous	-1.209	Destabilizing	0.25	N	0.672	neutral	None	None	None	None	N
E/V	0.487	ambiguous	0.4796	ambiguous	-0.385	Destabilizing	0.468	N	0.711	prob.delet.	D	0.633810412	None	None	N
E/W	0.9875	likely_pathogenic	0.9878	pathogenic	-0.566	Destabilizing	0.982	D	0.687	prob.neutral	None	None	None	None	N
E/Y	0.9293	likely_pathogenic	0.9242	pathogenic	-0.499	Destabilizing	0.826	D	0.756	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.