TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26802	80629;80630;80631	chr2:178565728;178565727;178565726	chr2:179430455;179430454;179430453
N2AB	25161	75706;75707;75708	chr2:178565728;178565727;178565726	chr2:179430455;179430454;179430453
N2A	24234	72925;72926;72927	chr2:178565728;178565727;178565726	chr2:179430455;179430454;179430453
N2B	17737	53434;53435;53436	chr2:178565728;178565727;178565726	chr2:179430455;179430454;179430453
Novex-1	17862	53809;53810;53811	chr2:178565728;178565727;178565726	chr2:179430455;179430454;179430453
Novex-2	17929	54010;54011;54012	chr2:178565728;178565727;178565726	chr2:179430455;179430454;179430453
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: Fn3-83
• Domain position: 23
• Structural Position: 25
• Q(SASA): 0.5289
• 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/A	rs201632545	-0.726	0.678	N	0.607	0.273	0.326074293725	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.92E-06	0
E/A	rs201632545	-0.726	0.678	N	0.607	0.273	0.326074293725	gnomAD-4.0.0	6.84285E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99572E-07	0	0
E/G	rs201632545	-1.205	0.778	N	0.646	0.296	None	gnomAD-2.1.1	2.93268E-04	None	None	None	None	N	None	0	0	None	0	0	None	0	None	2.63915E-03	1.01937E-04	4.21467E-04
E/G	rs201632545	-1.205	0.778	N	0.646	0.296	None	gnomAD-3.1.2	1.57845E-04	None	None	None	None	N	None	0	0	0	0	0	None	1.97777E-03	0	4.41E-05	0	0
E/G	rs201632545	-1.205	0.778	N	0.646	0.296	None	gnomAD-4.0.0	1.07845E-04	None	None	None	None	N	None	0	0	None	0	0	None	2.4055E-03	0	1.10204E-05	0	1.12126E-04
E/K	None	None	0.796	N	0.503	0.276	0.240491677333	gnomAD-4.0.0	1.36857E-06	None	None	None	None	N	None	0	0	None	0	0	None	1.87259E-05	0	8.9957E-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	0.3135	likely_benign	0.322	benign	-0.691	Destabilizing	0.678	D	0.607	neutral	N	0.483350295	None	None	N
E/C	0.913	likely_pathogenic	0.9235	pathogenic	-0.275	Destabilizing	0.996	D	0.744	deleterious	None	None	None	None	N
E/D	0.2011	likely_benign	0.1922	benign	-0.789	Destabilizing	0.001	N	0.257	neutral	N	0.481675427	None	None	N
E/F	0.9126	likely_pathogenic	0.9174	pathogenic	-0.477	Destabilizing	0.998	D	0.761	deleterious	None	None	None	None	N
E/G	0.259	likely_benign	0.2624	benign	-0.97	Destabilizing	0.778	D	0.646	neutral	N	0.490508341	None	None	N
E/H	0.7362	likely_pathogenic	0.7481	pathogenic	-0.614	Destabilizing	0.963	D	0.631	neutral	None	None	None	None	N
E/I	0.5365	ambiguous	0.6071	pathogenic	0.039	Stabilizing	0.945	D	0.772	deleterious	None	None	None	None	N
E/K	0.3465	ambiguous	0.3536	ambiguous	-0.348	Destabilizing	0.796	D	0.503	neutral	N	0.431611966	None	None	N
E/L	0.5414	ambiguous	0.5668	pathogenic	0.039	Stabilizing	0.945	D	0.768	deleterious	None	None	None	None	N
E/M	0.5845	likely_pathogenic	0.6265	pathogenic	0.368	Stabilizing	0.973	D	0.759	deleterious	None	None	None	None	N
E/N	0.4024	ambiguous	0.4023	ambiguous	-0.65	Destabilizing	0.008	N	0.366	neutral	None	None	None	None	N
E/P	0.8635	likely_pathogenic	0.8807	pathogenic	-0.183	Destabilizing	0.886	D	0.739	prob.delet.	None	None	None	None	N
E/Q	0.2041	likely_benign	0.2234	benign	-0.578	Destabilizing	0.907	D	0.611	neutral	N	0.475480173	None	None	N
E/R	0.5097	ambiguous	0.5206	ambiguous	-0.119	Destabilizing	0.948	D	0.631	neutral	None	None	None	None	N
E/S	0.3482	ambiguous	0.3658	ambiguous	-0.876	Destabilizing	0.583	D	0.499	neutral	None	None	None	None	N
E/T	0.3419	ambiguous	0.3808	ambiguous	-0.659	Destabilizing	0.794	D	0.694	prob.neutral	None	None	None	None	N
E/V	0.3246	likely_benign	0.3743	ambiguous	-0.183	Destabilizing	0.902	D	0.763	deleterious	N	0.493567288	None	None	N
E/W	0.9642	likely_pathogenic	0.9643	pathogenic	-0.313	Destabilizing	0.999	D	0.723	prob.delet.	None	None	None	None	N
E/Y	0.8391	likely_pathogenic	0.8443	pathogenic	-0.26	Destabilizing	0.997	D	0.768	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.