TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16442	49549;49550;49551	chr2:178614073;178614072;178614071	chr2:179478800;179478799;179478798
N2AB	14801	44626;44627;44628	chr2:178614073;178614072;178614071	chr2:179478800;179478799;179478798
N2A	13874	41845;41846;41847	chr2:178614073;178614072;178614071	chr2:179478800;179478799;179478798
N2B	7377	22354;22355;22356	chr2:178614073;178614072;178614071	chr2:179478800;179478799;179478798
Novex-1	7502	22729;22730;22731	chr2:178614073;178614072;178614071	chr2:179478800;179478799;179478798
Novex-2	7569	22930;22931;22932	chr2:178614073;178614072;178614071	chr2:179478800;179478799;179478798
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATA
• RefSeq wild type template codon: TAT
• Domain: Fn3-6
• Domain position: 92
• Structural Position: 127
• Q(SASA): 0.1786
• 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/M	None	None	0.39	N	0.41	0.065	0.367803931526	gnomAD-4.0.0	6.84796E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.16095E-05	0
I/V	rs2056850681	None	0.39	N	0.424	0.068	0.355450299083	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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	0.6635	likely_pathogenic	0.6369	pathogenic	-2.132	Highly Destabilizing	0.904	D	0.617	neutral	None	None	None	None	N
I/C	0.7579	likely_pathogenic	0.7436	pathogenic	-1.343	Destabilizing	0.999	D	0.735	deleterious	None	None	None	None	N
I/D	0.9828	likely_pathogenic	0.9756	pathogenic	-1.899	Destabilizing	0.995	D	0.898	deleterious	None	None	None	None	N
I/E	0.925	likely_pathogenic	0.9012	pathogenic	-1.731	Destabilizing	0.985	D	0.887	deleterious	None	None	None	None	N
I/F	0.2798	likely_benign	0.2399	benign	-1.224	Destabilizing	0.971	D	0.597	neutral	None	None	None	None	N
I/G	0.9312	likely_pathogenic	0.9148	pathogenic	-2.621	Highly Destabilizing	0.985	D	0.867	deleterious	None	None	None	None	N
I/H	0.8959	likely_pathogenic	0.8598	pathogenic	-1.827	Destabilizing	0.999	D	0.872	deleterious	None	None	None	None	N
I/K	0.8185	likely_pathogenic	0.7598	pathogenic	-1.587	Destabilizing	0.981	D	0.875	deleterious	N	0.47856743	None	None	N
I/L	0.1734	likely_benign	0.1546	benign	-0.764	Destabilizing	0.18	N	0.367	neutral	N	0.471370576	None	None	N
I/M	0.126	likely_benign	0.1181	benign	-0.63	Destabilizing	0.39	N	0.41	neutral	N	0.475478231	None	None	N
I/N	0.8606	likely_pathogenic	0.817	pathogenic	-1.761	Destabilizing	0.995	D	0.906	deleterious	None	None	None	None	N
I/P	0.988	likely_pathogenic	0.9844	pathogenic	-1.195	Destabilizing	0.995	D	0.905	deleterious	None	None	None	None	N
I/Q	0.805	likely_pathogenic	0.7565	pathogenic	-1.707	Destabilizing	0.985	D	0.898	deleterious	None	None	None	None	N
I/R	0.7918	likely_pathogenic	0.7217	pathogenic	-1.202	Destabilizing	0.981	D	0.904	deleterious	N	0.472753871	None	None	N
I/S	0.7859	likely_pathogenic	0.7454	pathogenic	-2.479	Highly Destabilizing	0.985	D	0.726	deleterious	None	None	None	None	N
I/T	0.5217	ambiguous	0.4905	ambiguous	-2.164	Highly Destabilizing	0.877	D	0.735	deleterious	N	0.458334824	None	None	N
I/V	0.0612	likely_benign	0.0622	benign	-1.195	Destabilizing	0.39	N	0.424	neutral	N	0.467631038	None	None	N
I/W	0.9526	likely_pathogenic	0.9412	pathogenic	-1.479	Destabilizing	0.999	D	0.865	deleterious	None	None	None	None	N
I/Y	0.8422	likely_pathogenic	0.7872	pathogenic	-1.19	Destabilizing	0.985	D	0.721	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.