TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15727	47404;47405;47406	chr2:178618279;178618278;178618277	chr2:179483006;179483005;179483004
N2AB	14086	42481;42482;42483	chr2:178618279;178618278;178618277	chr2:179483006;179483005;179483004
N2A	13159	39700;39701;39702	chr2:178618279;178618278;178618277	chr2:179483006;179483005;179483004
N2B	6662	20209;20210;20211	chr2:178618279;178618278;178618277	chr2:179483006;179483005;179483004
Novex-1	6787	20584;20585;20586	chr2:178618279;178618278;178618277	chr2:179483006;179483005;179483004
Novex-2	6854	20785;20786;20787	chr2:178618279;178618278;178618277	chr2:179483006;179483005;179483004
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Fn3-1
• Domain position: 71
• Structural Position: 103
• Q(SASA): 0.2215
• 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/G	rs1342638829	-1.278	0.959	N	0.533	0.264	0.371157983038	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
E/G	rs1342638829	-1.278	0.959	N	0.533	0.264	0.371157983038	gnomAD-4.0.0	1.59328E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43332E-05	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	0.2036	likely_benign	0.2361	benign	-0.656	Destabilizing	0.826	D	0.408	neutral	N	0.481324974	None	None	N
E/C	0.8686	likely_pathogenic	0.8472	pathogenic	-0.388	Destabilizing	0.999	D	0.621	neutral	None	None	None	None	N
E/D	0.2766	likely_benign	0.391	ambiguous	-1.069	Destabilizing	0.959	D	0.445	neutral	N	0.484136203	None	None	N
E/F	0.8343	likely_pathogenic	0.8672	pathogenic	0.157	Stabilizing	0.046	N	0.437	neutral	None	None	None	None	N
E/G	0.3032	likely_benign	0.3797	ambiguous	-1.076	Destabilizing	0.959	D	0.533	neutral	N	0.481724233	None	None	N
E/H	0.6533	likely_pathogenic	0.7086	pathogenic	-0.138	Destabilizing	0.997	D	0.563	neutral	None	None	None	None	N
E/I	0.5196	ambiguous	0.5755	pathogenic	0.509	Stabilizing	0.884	D	0.538	neutral	None	None	None	None	N
E/K	0.2732	likely_benign	0.3583	ambiguous	-0.58	Destabilizing	0.134	N	0.174	neutral	N	0.449271542	None	None	N
E/L	0.4599	ambiguous	0.534	ambiguous	0.509	Stabilizing	0.02	N	0.424	neutral	None	None	None	None	N
E/M	0.5182	ambiguous	0.5667	pathogenic	0.908	Stabilizing	0.579	D	0.354	neutral	None	None	None	None	N
E/N	0.4015	ambiguous	0.5031	ambiguous	-1.174	Destabilizing	0.969	D	0.545	neutral	None	None	None	None	N
E/P	0.6028	likely_pathogenic	0.6443	pathogenic	0.143	Stabilizing	0.997	D	0.627	neutral	None	None	None	None	N
E/Q	0.1658	likely_benign	0.1879	benign	-0.965	Destabilizing	0.92	D	0.511	neutral	N	0.483119748	None	None	N
E/R	0.3911	ambiguous	0.4668	ambiguous	-0.294	Destabilizing	0.884	D	0.501	neutral	None	None	None	None	N
E/S	0.2575	likely_benign	0.3037	benign	-1.531	Destabilizing	0.939	D	0.431	neutral	None	None	None	None	N
E/T	0.2796	likely_benign	0.3189	benign	-1.17	Destabilizing	0.969	D	0.485	neutral	None	None	None	None	N
E/V	0.3161	likely_benign	0.371	ambiguous	0.143	Stabilizing	0.704	D	0.475	neutral	N	0.486630245	None	None	N
E/W	0.938	likely_pathogenic	0.9499	pathogenic	0.41	Stabilizing	0.999	D	0.623	neutral	None	None	None	None	N
E/Y	0.7594	likely_pathogenic	0.8041	pathogenic	0.424	Stabilizing	0.964	D	0.626	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.