TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18874	56845;56846;56847	chr2:178599173;178599172;178599171	chr2:179463900;179463899;179463898
N2AB	17233	51922;51923;51924	chr2:178599173;178599172;178599171	chr2:179463900;179463899;179463898
N2A	16306	49141;49142;49143	chr2:178599173;178599172;178599171	chr2:179463900;179463899;179463898
N2B	9809	29650;29651;29652	chr2:178599173;178599172;178599171	chr2:179463900;179463899;179463898
Novex-1	9934	30025;30026;30027	chr2:178599173;178599172;178599171	chr2:179463900;179463899;179463898
Novex-2	10001	30226;30227;30228	chr2:178599173;178599172;178599171	chr2:179463900;179463899;179463898
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: Fn3-24
• Domain position: 91
• Structural Position: 125
• Q(SASA): 0.2297
• 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/D	None	None	0.007	N	0.347	0.05	0.198526703765	gnomAD-4.0.0	1.47445E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.87813E-06	0	0
E/K	rs781465190	-0.156	0.518	N	0.441	0.12	0.260735089382	gnomAD-2.1.1	5.87E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.18E-05	0
E/K	rs781465190	-0.156	0.518	N	0.441	0.12	0.260735089382	gnomAD-4.0.0	7.38197E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.39894E-07	0	0
E/Q	None	None	0.062	N	0.295	0.098	0.237489013734	gnomAD-4.0.0	7.38197E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.39894E-07	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
E/A	0.1273	likely_benign	0.1229	benign	-0.157	Destabilizing	0.518	D	0.513	neutral	N	0.506933657	None	None	N
E/C	0.7355	likely_pathogenic	0.7277	pathogenic	-0.216	Destabilizing	0.996	D	0.663	prob.neutral	None	None	None	None	N
E/D	0.1084	likely_benign	0.1028	benign	-0.288	Destabilizing	0.007	N	0.347	neutral	N	0.451619091	None	None	N
E/F	0.625	likely_pathogenic	0.6187	pathogenic	-0.006	Destabilizing	0.996	D	0.733	deleterious	None	None	None	None	N
E/G	0.1572	likely_benign	0.1456	benign	-0.319	Destabilizing	0.682	D	0.659	prob.neutral	N	0.485154172	None	None	N
E/H	0.3969	ambiguous	0.3982	ambiguous	0.544	Stabilizing	0.974	D	0.616	neutral	None	None	None	None	N
E/I	0.2244	likely_benign	0.2151	benign	0.225	Stabilizing	0.953	D	0.78	deleterious	None	None	None	None	N
E/K	0.1037	likely_benign	0.1012	benign	0.427	Stabilizing	0.518	D	0.441	neutral	N	0.507800448	None	None	N
E/L	0.2488	likely_benign	0.242	benign	0.225	Stabilizing	0.909	D	0.755	deleterious	None	None	None	None	N
E/M	0.3157	likely_benign	0.3082	benign	0.043	Stabilizing	0.987	D	0.694	prob.delet.	None	None	None	None	N
E/N	0.2059	likely_benign	0.1995	benign	0.012	Stabilizing	0.909	D	0.629	neutral	None	None	None	None	N
E/P	0.2941	likely_benign	0.289	benign	0.117	Stabilizing	0.953	D	0.665	prob.neutral	None	None	None	None	N
E/Q	0.1183	likely_benign	0.1196	benign	0.058	Stabilizing	0.062	N	0.295	neutral	N	0.501951911	None	None	N
E/R	0.2145	likely_benign	0.2175	benign	0.721	Stabilizing	0.833	D	0.595	neutral	None	None	None	None	N
E/S	0.1661	likely_benign	0.1637	benign	-0.114	Destabilizing	0.587	D	0.514	neutral	None	None	None	None	N
E/T	0.1862	likely_benign	0.1797	benign	0.031	Stabilizing	0.909	D	0.683	prob.neutral	None	None	None	None	N
E/V	0.1486	likely_benign	0.1402	benign	0.117	Stabilizing	0.883	D	0.735	deleterious	N	0.476253402	None	None	N
E/W	0.8546	likely_pathogenic	0.8531	pathogenic	0.121	Stabilizing	0.996	D	0.65	prob.neutral	None	None	None	None	N
E/Y	0.5123	ambiguous	0.5089	ambiguous	0.238	Stabilizing	0.953	D	0.741	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.