TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26126	78601;78602;78603	chr2:178567756;178567755;178567754	chr2:179432483;179432482;179432481
N2AB	24485	73678;73679;73680	chr2:178567756;178567755;178567754	chr2:179432483;179432482;179432481
N2A	23558	70897;70898;70899	chr2:178567756;178567755;178567754	chr2:179432483;179432482;179432481
N2B	17061	51406;51407;51408	chr2:178567756;178567755;178567754	chr2:179432483;179432482;179432481
Novex-1	17186	51781;51782;51783	chr2:178567756;178567755;178567754	chr2:179432483;179432482;179432481
Novex-2	17253	51982;51983;51984	chr2:178567756;178567755;178567754	chr2:179432483;179432482;179432481
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: Fn3-78
• Domain position: 39
• Structural Position: 41
• Q(SASA): 0.0979
• 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/Q	rs1325081624	-1.65	1.0	N	0.747	0.363	0.277730125212	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
E/Q	rs1325081624	-1.65	1.0	N	0.747	0.363	0.277730125212	gnomAD-4.0.0	1.59236E-06	None	None	None	None	N	None	0	2.2877E-05	None	0	0	None	0	0	0	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	0.9627	likely_pathogenic	0.9615	pathogenic	-1.815	Destabilizing	0.999	D	0.735	prob.delet.	D	0.556751952	None	None	N
E/C	0.9932	likely_pathogenic	0.9927	pathogenic	-0.955	Destabilizing	1.0	D	0.816	deleterious	None	None	None	None	N
E/D	0.9723	likely_pathogenic	0.974	pathogenic	-1.912	Destabilizing	0.999	D	0.668	neutral	N	0.497590569	None	None	N
E/F	0.9971	likely_pathogenic	0.9971	pathogenic	-1.525	Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
E/G	0.9703	likely_pathogenic	0.97	pathogenic	-2.184	Highly Destabilizing	1.0	D	0.801	deleterious	D	0.540422124	None	None	N
E/H	0.9931	likely_pathogenic	0.9932	pathogenic	-1.35	Destabilizing	1.0	D	0.73	prob.delet.	None	None	None	None	N
E/I	0.9904	likely_pathogenic	0.9896	pathogenic	-0.743	Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
E/K	0.9777	likely_pathogenic	0.9765	pathogenic	-1.806	Destabilizing	0.999	D	0.67	neutral	D	0.53260731	None	None	N
E/L	0.9893	likely_pathogenic	0.9889	pathogenic	-0.743	Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
E/M	0.9859	likely_pathogenic	0.985	pathogenic	0.005	Stabilizing	1.0	D	0.804	deleterious	None	None	None	None	N
E/N	0.9942	likely_pathogenic	0.9944	pathogenic	-1.993	Destabilizing	1.0	D	0.774	deleterious	None	None	None	None	N
E/P	0.9998	likely_pathogenic	0.9998	pathogenic	-1.089	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
E/Q	0.839	likely_pathogenic	0.8412	pathogenic	-1.698	Destabilizing	1.0	D	0.747	deleterious	N	0.479104239	None	None	N
E/R	0.9834	likely_pathogenic	0.9821	pathogenic	-1.599	Destabilizing	1.0	D	0.768	deleterious	None	None	None	None	N
E/S	0.9712	likely_pathogenic	0.971	pathogenic	-2.613	Highly Destabilizing	0.999	D	0.717	prob.delet.	None	None	None	None	N
E/T	0.9876	likely_pathogenic	0.9878	pathogenic	-2.257	Highly Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
E/V	0.9772	likely_pathogenic	0.9751	pathogenic	-1.089	Destabilizing	1.0	D	0.809	deleterious	D	0.534635226	None	None	N
E/W	0.9984	likely_pathogenic	0.9983	pathogenic	-1.624	Destabilizing	1.0	D	0.816	deleterious	None	None	None	None	N
E/Y	0.9943	likely_pathogenic	0.9943	pathogenic	-1.368	Destabilizing	1.0	D	0.825	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.