TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5496	16711;16712;16713	chr2:178732575;178732574;178732573	chr2:179597302;179597301;179597300
N2AB	5179	15760;15761;15762	chr2:178732575;178732574;178732573	chr2:179597302;179597301;179597300
N2A	4252	12979;12980;12981	chr2:178732575;178732574;178732573	chr2:179597302;179597301;179597300
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: C
• RefSeq wild type transcript codon: TGC
• RefSeq wild type template codon: ACG
• Domain: Ig-38
• Domain position: 47
• Structural Position: 121
• Q(SASA): 0.1668
• 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
C/Y	rs373848201	-1.371	0.116	N	0.439	0.279	None	gnomAD-2.1.1	8.06E-06	None	None	None	None	N	None	1.29316E-04	0	None	0	0	None	0	None	0	0	0
C/Y	rs373848201	-1.371	0.116	N	0.439	0.279	None	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
C/Y	rs373848201	-1.371	0.116	N	0.439	0.279	None	gnomAD-4.0.0	2.56283E-06	None	None	None	None	N	None	3.38375E-05	0	None	0	0	None	0	0	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
C/A	0.5073	ambiguous	0.5858	pathogenic	-1.498	Destabilizing	0.963	D	0.572	neutral	None	None	None	None	N
C/D	0.8136	likely_pathogenic	0.9059	pathogenic	0.474	Stabilizing	0.999	D	0.676	prob.neutral	None	None	None	None	N
C/E	0.8702	likely_pathogenic	0.9324	pathogenic	0.614	Stabilizing	0.999	D	0.672	neutral	None	None	None	None	N
C/F	0.1979	likely_benign	0.2397	benign	-0.957	Destabilizing	0.921	D	0.619	neutral	N	0.42392635	None	None	N
C/G	0.2803	likely_benign	0.3669	ambiguous	-1.816	Destabilizing	0.993	D	0.654	neutral	N	0.485092239	None	None	N
C/H	0.5225	ambiguous	0.612	pathogenic	-1.878	Destabilizing	0.991	D	0.675	neutral	None	None	None	None	N
C/I	0.4251	ambiguous	0.4893	ambiguous	-0.675	Destabilizing	0.984	D	0.618	neutral	None	None	None	None	N
C/K	0.8419	likely_pathogenic	0.9151	pathogenic	-0.181	Destabilizing	0.995	D	0.669	neutral	None	None	None	None	N
C/L	0.494	ambiguous	0.5748	pathogenic	-0.675	Destabilizing	0.927	D	0.591	neutral	None	None	None	None	N
C/M	0.6853	likely_pathogenic	0.7412	pathogenic	-0.062	Destabilizing	0.999	D	0.631	neutral	None	None	None	None	N
C/N	0.6071	likely_pathogenic	0.7259	pathogenic	-0.318	Destabilizing	0.999	D	0.692	prob.neutral	None	None	None	None	N
C/P	0.9212	likely_pathogenic	0.968	pathogenic	-0.923	Destabilizing	0.999	D	0.693	prob.neutral	None	None	None	None	N
C/Q	0.6825	likely_pathogenic	0.7874	pathogenic	-0.074	Destabilizing	0.999	D	0.695	prob.neutral	None	None	None	None	N
C/R	0.455	ambiguous	0.5932	pathogenic	-0.436	Destabilizing	0.994	D	0.695	prob.neutral	N	0.474221884	None	None	N
C/S	0.3562	ambiguous	0.4384	ambiguous	-0.894	Destabilizing	0.979	D	0.613	neutral	N	0.491018134	None	None	N
C/T	0.4815	ambiguous	0.5517	ambiguous	-0.543	Destabilizing	0.984	D	0.62	neutral	None	None	None	None	N
C/V	0.4084	ambiguous	0.4363	ambiguous	-0.923	Destabilizing	0.969	D	0.606	neutral	None	None	None	None	N
C/W	0.4836	ambiguous	0.5617	ambiguous	-0.97	Destabilizing	0.999	D	0.617	neutral	N	0.514068352	None	None	N
C/Y	0.2443	likely_benign	0.2874	benign	-0.882	Destabilizing	0.116	N	0.439	neutral	N	0.419461893	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.