TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26581	79966;79967;79968	chr2:178566391;178566390;178566389	chr2:179431118;179431117;179431116
N2AB	24940	75043;75044;75045	chr2:178566391;178566390;178566389	chr2:179431118;179431117;179431116
N2A	24013	72262;72263;72264	chr2:178566391;178566390;178566389	chr2:179431118;179431117;179431116
N2B	17516	52771;52772;52773	chr2:178566391;178566390;178566389	chr2:179431118;179431117;179431116
Novex-1	17641	53146;53147;53148	chr2:178566391;178566390;178566389	chr2:179431118;179431117;179431116
Novex-2	17708	53347;53348;53349	chr2:178566391;178566390;178566389	chr2:179431118;179431117;179431116
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Fn3-81
• Domain position: 95
• Structural Position: 127
• Q(SASA): 0.2472
• 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
V/G	None	None	0.994	N	0.793	0.511	0.765723535249	gnomAD-4.0.0	1.59183E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85884E-06	0	0
V/M	None	None	0.961	N	0.69	0.255	0.530803083455	gnomAD-4.0.0	1.59189E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85884E-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
V/A	0.1617	likely_benign	0.1579	benign	-1.899	Destabilizing	0.877	D	0.58	neutral	N	0.517639013	None	None	N
V/C	0.5952	likely_pathogenic	0.6027	pathogenic	-1.404	Destabilizing	0.999	D	0.729	deleterious	None	None	None	None	N
V/D	0.6831	likely_pathogenic	0.6586	pathogenic	-2.08	Highly Destabilizing	0.995	D	0.826	deleterious	None	None	None	None	N
V/E	0.5152	ambiguous	0.4822	ambiguous	-1.925	Destabilizing	0.994	D	0.782	deleterious	N	0.51915995	None	None	N
V/F	0.1836	likely_benign	0.1895	benign	-1.171	Destabilizing	0.971	D	0.774	deleterious	None	None	None	None	N
V/G	0.291	likely_benign	0.2781	benign	-2.385	Highly Destabilizing	0.994	D	0.793	deleterious	N	0.51915995	None	None	N
V/H	0.6486	likely_pathogenic	0.6317	pathogenic	-1.921	Destabilizing	0.999	D	0.806	deleterious	None	None	None	None	N
V/I	0.0735	likely_benign	0.0769	benign	-0.587	Destabilizing	0.029	N	0.233	neutral	None	None	None	None	N
V/K	0.5232	ambiguous	0.4879	ambiguous	-1.648	Destabilizing	0.985	D	0.775	deleterious	None	None	None	None	N
V/L	0.1839	likely_benign	0.1948	benign	-0.587	Destabilizing	0.022	N	0.286	neutral	N	0.515864587	None	None	N
V/M	0.1521	likely_benign	0.1555	benign	-0.524	Destabilizing	0.961	D	0.69	prob.delet.	N	0.507296666	None	None	N
V/N	0.4883	ambiguous	0.4746	ambiguous	-1.787	Destabilizing	0.995	D	0.815	deleterious	None	None	None	None	N
V/P	0.6533	likely_pathogenic	0.6256	pathogenic	-0.993	Destabilizing	0.995	D	0.792	deleterious	None	None	None	None	N
V/Q	0.44	ambiguous	0.4211	ambiguous	-1.74	Destabilizing	0.995	D	0.782	deleterious	None	None	None	None	N
V/R	0.4593	ambiguous	0.4417	ambiguous	-1.308	Destabilizing	0.995	D	0.818	deleterious	None	None	None	None	N
V/S	0.2926	likely_benign	0.2833	benign	-2.422	Highly Destabilizing	0.985	D	0.746	deleterious	None	None	None	None	N
V/T	0.2109	likely_benign	0.2079	benign	-2.125	Highly Destabilizing	0.904	D	0.659	prob.neutral	None	None	None	None	N
V/W	0.8006	likely_pathogenic	0.8051	pathogenic	-1.552	Destabilizing	0.999	D	0.705	prob.delet.	None	None	None	None	N
V/Y	0.5354	ambiguous	0.5545	ambiguous	-1.188	Destabilizing	0.995	D	0.731	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.