TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8811	26656;26657;26658	chr2:178714343;178714342;178714341	chr2:179579070;179579069;179579068
N2AB	8494	25705;25706;25707	chr2:178714343;178714342;178714341	chr2:179579070;179579069;179579068
N2A	7567	22924;22925;22926	chr2:178714343;178714342;178714341	chr2:179579070;179579069;179579068
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: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Ig-73
• Domain position: 76
• Structural Position: 158
• Q(SASA): 0.0417
• 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
I/V	rs1346764958	-2.293	0.001	N	0.261	0.104	0.327419511103	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.9E-06	0
I/V	rs1346764958	-2.293	0.001	N	0.261	0.104	0.327419511103	gnomAD-4.0.0	4.8013E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.25002E-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
I/A	0.4198	ambiguous	0.5459	ambiguous	-2.967	Highly Destabilizing	0.839	D	0.689	prob.neutral	None	None	None	None	N
I/C	0.8146	likely_pathogenic	0.8838	pathogenic	-2.187	Highly Destabilizing	1.0	D	0.79	deleterious	None	None	None	None	N
I/D	0.9804	likely_pathogenic	0.994	pathogenic	-3.622	Highly Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
I/E	0.9528	likely_pathogenic	0.9832	pathogenic	-3.369	Highly Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
I/F	0.4256	ambiguous	0.597	pathogenic	-1.693	Destabilizing	0.986	D	0.75	deleterious	N	0.50501526	None	None	N
I/G	0.799	likely_pathogenic	0.9045	pathogenic	-3.5	Highly Destabilizing	0.994	D	0.818	deleterious	None	None	None	None	N
I/H	0.9534	likely_pathogenic	0.9846	pathogenic	-2.949	Highly Destabilizing	0.999	D	0.825	deleterious	None	None	None	None	N
I/K	0.932	likely_pathogenic	0.9753	pathogenic	-2.351	Highly Destabilizing	0.994	D	0.821	deleterious	None	None	None	None	N
I/L	0.1472	likely_benign	0.2056	benign	-1.385	Destabilizing	None	N	0.301	neutral	N	0.465295757	None	None	N
I/M	0.1291	likely_benign	0.1748	benign	-1.438	Destabilizing	0.565	D	0.709	prob.delet.	N	0.486911005	None	None	N
I/N	0.7888	likely_pathogenic	0.9061	pathogenic	-2.818	Highly Destabilizing	1.0	D	0.848	deleterious	N	0.50526875	None	None	N
I/P	0.9828	likely_pathogenic	0.9944	pathogenic	-1.901	Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
I/Q	0.909	likely_pathogenic	0.9658	pathogenic	-2.627	Highly Destabilizing	1.0	D	0.842	deleterious	None	None	None	None	N
I/R	0.8936	likely_pathogenic	0.96	pathogenic	-2.042	Highly Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
I/S	0.6085	likely_pathogenic	0.7668	pathogenic	-3.41	Highly Destabilizing	0.993	D	0.792	deleterious	D	0.533694262	None	None	N
I/T	0.5266	ambiguous	0.7101	pathogenic	-3.029	Highly Destabilizing	0.851	D	0.743	deleterious	D	0.527768368	None	None	N
I/V	0.0838	likely_benign	0.1105	benign	-1.901	Destabilizing	0.001	N	0.261	neutral	N	0.421960693	None	None	N
I/W	0.9622	likely_pathogenic	0.9855	pathogenic	-2.155	Highly Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
I/Y	0.8715	likely_pathogenic	0.9378	pathogenic	-1.961	Destabilizing	0.962	D	0.809	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.