TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27852	83779;83780;83781	chr2:178562578;178562577;178562576	chr2:179427305;179427304;179427303
N2AB	26211	78856;78857;78858	chr2:178562578;178562577;178562576	chr2:179427305;179427304;179427303
N2A	25284	76075;76076;76077	chr2:178562578;178562577;178562576	chr2:179427305;179427304;179427303
N2B	18787	56584;56585;56586	chr2:178562578;178562577;178562576	chr2:179427305;179427304;179427303
Novex-1	18912	56959;56960;56961	chr2:178562578;178562577;178562576	chr2:179427305;179427304;179427303
Novex-2	18979	57160;57161;57162	chr2:178562578;178562577;178562576	chr2:179427305;179427304;179427303
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCT
• RefSeq wild type template codon: CGA
• Domain: Fn3-90
• Domain position: 87
• Structural Position: 121
• Q(SASA): 0.1357
• Predicted PPI site: I

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
A/D	None	None	0.996	N	0.758	0.435	0.616786663822	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
A/D	None	None	0.996	N	0.758	0.435	0.616786663822	gnomAD-4.0.0	6.57315E-06	None	None	None	None	I	None	2.41278E-05	0	None	0	0	None	0	0	0	0	0
A/G	rs541476378	None	0.873	N	0.581	0.255	0.280987212366	gnomAD-4.0.0	3.60097E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	3.9375E-06	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
A/C	0.3749	ambiguous	0.356	ambiguous	-1.127	Destabilizing	1.0	D	0.755	deleterious	None	None	None	None	I
A/D	0.7798	likely_pathogenic	0.7275	pathogenic	-1.873	Destabilizing	0.996	D	0.758	deleterious	N	0.491924894	None	None	I
A/E	0.59	likely_pathogenic	0.555	ambiguous	-1.847	Destabilizing	0.998	D	0.713	prob.delet.	None	None	None	None	I
A/F	0.5191	ambiguous	0.4894	ambiguous	-1.07	Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	I
A/G	0.1889	likely_benign	0.1982	benign	-1.522	Destabilizing	0.873	D	0.581	neutral	N	0.468033741	None	None	I
A/H	0.7449	likely_pathogenic	0.6989	pathogenic	-1.718	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	I
A/I	0.2614	likely_benign	0.2513	benign	-0.448	Destabilizing	0.998	D	0.742	deleterious	None	None	None	None	I
A/K	0.7077	likely_pathogenic	0.6754	pathogenic	-1.59	Destabilizing	0.999	D	0.716	prob.delet.	None	None	None	None	I
A/L	0.2757	likely_benign	0.2613	benign	-0.448	Destabilizing	0.994	D	0.627	neutral	None	None	None	None	I
A/M	0.2564	likely_benign	0.2534	benign	-0.4	Destabilizing	1.0	D	0.771	deleterious	None	None	None	None	I
A/N	0.5752	likely_pathogenic	0.5251	ambiguous	-1.412	Destabilizing	0.975	D	0.773	deleterious	None	None	None	None	I
A/P	0.9528	likely_pathogenic	0.9524	pathogenic	-0.658	Destabilizing	0.998	D	0.748	deleterious	N	0.491417915	None	None	I
A/Q	0.5368	ambiguous	0.511	ambiguous	-1.511	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	I
A/R	0.6109	likely_pathogenic	0.586	pathogenic	-1.25	Destabilizing	0.999	D	0.763	deleterious	None	None	None	None	I
A/S	0.1277	likely_benign	0.1151	benign	-1.761	Destabilizing	0.722	D	0.557	neutral	N	0.398002745	None	None	I
A/T	0.0999	likely_benign	0.0971	benign	-1.644	Destabilizing	0.25	N	0.387	neutral	N	0.488115822	None	None	I
A/V	0.1165	likely_benign	0.1146	benign	-0.658	Destabilizing	0.98	D	0.577	neutral	N	0.499063535	None	None	I
A/W	0.8943	likely_pathogenic	0.8766	pathogenic	-1.523	Destabilizing	1.0	D	0.834	deleterious	None	None	None	None	I
A/Y	0.7162	likely_pathogenic	0.6808	pathogenic	-1.115	Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	I

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.