TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8760	26503;26504;26505	chr2:178714496;178714495;178714494	chr2:179579223;179579222;179579221
N2AB	8443	25552;25553;25554	chr2:178714496;178714495;178714494	chr2:179579223;179579222;179579221
N2A	7516	22771;22772;22773	chr2:178714496;178714495;178714494	chr2:179579223;179579222;179579221
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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-73
• Domain position: 25
• Structural Position: 38
• Q(SASA): 0.3516
• 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	rs2077161238	None	0.001	N	0.108	0.182	0.229924730088	gnomAD-4.0.0	1.77937E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.33896E-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	0.1317	likely_benign	0.1691	benign	-0.495	Destabilizing	0.025	N	0.32	neutral	N	0.494637229	None	None	N
E/C	0.8287	likely_pathogenic	0.8926	pathogenic	-0.162	Destabilizing	0.93	D	0.474	neutral	None	None	None	None	N
E/D	0.1837	likely_benign	0.2211	benign	-0.523	Destabilizing	0.006	N	0.283	neutral	D	0.536542566	None	None	N
E/F	0.6987	likely_pathogenic	0.7755	pathogenic	-0.195	Destabilizing	0.867	D	0.433	neutral	None	None	None	None	N
E/G	0.1979	likely_benign	0.2917	benign	-0.736	Destabilizing	0.289	N	0.35	neutral	N	0.497813238	None	None	N
E/H	0.3729	ambiguous	0.4511	ambiguous	-0.024	Destabilizing	0.43	N	0.352	neutral	None	None	None	None	N
E/I	0.3133	likely_benign	0.3831	ambiguous	0.123	Stabilizing	0.5	N	0.46	neutral	None	None	None	None	N
E/K	0.1134	likely_benign	0.1563	benign	0.213	Stabilizing	0.001	N	0.108	neutral	N	0.461524733	None	None	N
E/L	0.3499	ambiguous	0.4386	ambiguous	0.123	Stabilizing	0.123	N	0.416	neutral	None	None	None	None	N
E/M	0.4032	ambiguous	0.4962	ambiguous	0.235	Stabilizing	0.403	N	0.412	neutral	None	None	None	None	N
E/N	0.3201	likely_benign	0.3977	ambiguous	-0.245	Destabilizing	0.061	N	0.293	neutral	None	None	None	None	N
E/P	0.9246	likely_pathogenic	0.9601	pathogenic	-0.062	Destabilizing	0.129	N	0.357	neutral	None	None	None	None	N
E/Q	0.1088	likely_benign	0.1259	benign	-0.195	Destabilizing	0.001	N	0.179	neutral	N	0.486252669	None	None	N
E/R	0.1909	likely_benign	0.2557	benign	0.48	Stabilizing	0.131	N	0.261	neutral	None	None	None	None	N
E/S	0.1788	likely_benign	0.2177	benign	-0.412	Destabilizing	0.006	N	0.151	neutral	None	None	None	None	N
E/T	0.1791	likely_benign	0.2184	benign	-0.212	Destabilizing	0.101	N	0.309	neutral	None	None	None	None	N
E/V	0.1902	likely_benign	0.2345	benign	-0.062	Destabilizing	0.07	N	0.371	neutral	N	0.49055831	None	None	N
E/W	0.8407	likely_pathogenic	0.8983	pathogenic	0.025	Stabilizing	0.985	D	0.557	neutral	None	None	None	None	N
E/Y	0.5813	likely_pathogenic	0.6776	pathogenic	0.069	Stabilizing	0.851	D	0.424	neutral	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.