TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27536	82831;82832;82833	chr2:178563526;178563525;178563524	chr2:179428253;179428252;179428251
N2AB	25895	77908;77909;77910	chr2:178563526;178563525;178563524	chr2:179428253;179428252;179428251
N2A	24968	75127;75128;75129	chr2:178563526;178563525;178563524	chr2:179428253;179428252;179428251
N2B	18471	55636;55637;55638	chr2:178563526;178563525;178563524	chr2:179428253;179428252;179428251
Novex-1	18596	56011;56012;56013	chr2:178563526;178563525;178563524	chr2:179428253;179428252;179428251
Novex-2	18663	56212;56213;56214	chr2:178563526;178563525;178563524	chr2:179428253;179428252;179428251
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: Fn3-88
• Domain position: 68
• Structural Position: 99
• Q(SASA): 0.4261
• 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	rs745974517	0.062	0.989	N	0.58	0.339	0.383590876969	gnomAD-2.1.1	3.62E-05	None	None	None	None	N	None	1.29182E-04	0	None	0	2.22941E-04	None	3.27E-05	None	4.64E-05	8.88E-06	0
E/K	rs745974517	0.062	0.989	N	0.58	0.339	0.383590876969	gnomAD-4.0.0	1.09474E-05	None	None	None	None	N	None	5.97693E-05	0	None	0	1.00806E-04	None	1.87259E-05	1.7343E-04	3.59789E-06	2.31868E-05	3.31345E-05

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	0.1492	likely_benign	0.1635	benign	-0.474	Destabilizing	0.939	D	0.535	neutral	N	0.476506892	None	None	N
E/C	0.8616	likely_pathogenic	0.8814	pathogenic	0.029	Stabilizing	0.999	D	0.703	prob.neutral	None	None	None	None	N
E/D	0.1417	likely_benign	0.2139	benign	-0.645	Destabilizing	0.02	N	0.147	neutral	N	0.496349574	None	None	N
E/F	0.8675	likely_pathogenic	0.8933	pathogenic	-0.571	Destabilizing	0.999	D	0.675	prob.neutral	None	None	None	None	N
E/G	0.2578	likely_benign	0.3092	benign	-0.704	Destabilizing	0.939	D	0.541	neutral	N	0.507959369	None	None	N
E/H	0.5794	likely_pathogenic	0.6397	pathogenic	-0.702	Destabilizing	0.999	D	0.592	neutral	None	None	None	None	N
E/I	0.514	ambiguous	0.5074	ambiguous	0.104	Stabilizing	0.993	D	0.701	prob.neutral	None	None	None	None	N
E/K	0.2295	likely_benign	0.263	benign	-0.005	Destabilizing	0.989	D	0.58	neutral	N	0.486777241	None	None	N
E/L	0.5742	likely_pathogenic	0.6168	pathogenic	0.104	Stabilizing	0.993	D	0.675	prob.neutral	None	None	None	None	N
E/M	0.6234	likely_pathogenic	0.6268	pathogenic	0.455	Stabilizing	0.999	D	0.633	neutral	None	None	None	None	N
E/N	0.3137	likely_benign	0.3678	ambiguous	-0.173	Destabilizing	0.973	D	0.597	neutral	None	None	None	None	N
E/P	0.3413	ambiguous	0.3679	ambiguous	-0.067	Destabilizing	0.993	D	0.583	neutral	None	None	None	None	N
E/Q	0.1962	likely_benign	0.2025	benign	-0.159	Destabilizing	0.996	D	0.629	neutral	N	0.482093207	None	None	N
E/R	0.351	ambiguous	0.3881	ambiguous	0.086	Stabilizing	0.993	D	0.613	neutral	None	None	None	None	N
E/S	0.2219	likely_benign	0.2537	benign	-0.382	Destabilizing	0.953	D	0.561	neutral	None	None	None	None	N
E/T	0.312	likely_benign	0.3245	benign	-0.21	Destabilizing	0.986	D	0.553	neutral	None	None	None	None	N
E/V	0.2973	likely_benign	0.2977	benign	-0.067	Destabilizing	0.991	D	0.628	neutral	N	0.496349574	None	None	N
E/W	0.95	likely_pathogenic	0.9627	pathogenic	-0.504	Destabilizing	0.999	D	0.701	prob.neutral	None	None	None	None	N
E/Y	0.7544	likely_pathogenic	0.808	pathogenic	-0.356	Destabilizing	0.999	D	0.643	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.