TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5789	17590;17591;17592	chr2:178731401;178731400;178731399	chr2:179596128;179596127;179596126
N2AB	5472	16639;16640;16641	chr2:178731401;178731400;178731399	chr2:179596128;179596127;179596126
N2A	4545	13858;13859;13860	chr2:178731401;178731400;178731399	chr2:179596128;179596127;179596126
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTC
• RefSeq wild type template codon: GAG
• Domain: Ig-41
• Domain position: 60
• Structural Position: 140
• Q(SASA): 0.0919
• 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
L/F	None	None	0.175	N	0.665	0.264	0.530948259028	gnomAD-4.0.0	3.18241E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.71631E-06	0	0
L/V	rs778228033	-1.413	None	N	0.317	0.134	0.468586609112	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
L/V	rs778228033	-1.413	None	N	0.317	0.134	0.468586609112	gnomAD-4.0.0	1.59121E-06	None	None	None	None	N	None	0	2.28666E-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
L/A	0.7207	likely_pathogenic	0.7345	pathogenic	-2.946	Highly Destabilizing	0.055	N	0.536	neutral	None	None	None	None	N
L/C	0.675	likely_pathogenic	0.6655	pathogenic	-2.474	Highly Destabilizing	0.958	D	0.751	deleterious	None	None	None	None	N
L/D	0.9867	likely_pathogenic	0.9868	pathogenic	-3.491	Highly Destabilizing	0.667	D	0.79	deleterious	None	None	None	None	N
L/E	0.9398	likely_pathogenic	0.9417	pathogenic	-3.227	Highly Destabilizing	0.22	N	0.72	prob.delet.	None	None	None	None	N
L/F	0.1541	likely_benign	0.1578	benign	-1.838	Destabilizing	0.175	N	0.665	neutral	N	0.464431752	None	None	N
L/G	0.9336	likely_pathogenic	0.9375	pathogenic	-3.547	Highly Destabilizing	0.364	N	0.734	prob.delet.	None	None	None	None	N
L/H	0.756	likely_pathogenic	0.7601	pathogenic	-3.073	Highly Destabilizing	0.002	N	0.588	neutral	D	0.534697127	None	None	N
L/I	0.0653	likely_benign	0.0639	benign	-1.179	Destabilizing	None	N	0.279	neutral	N	0.329308743	None	None	N
L/K	0.9037	likely_pathogenic	0.9051	pathogenic	-2.519	Highly Destabilizing	0.004	N	0.533	neutral	None	None	None	None	N
L/M	0.1545	likely_benign	0.1541	benign	-1.198	Destabilizing	0.497	N	0.635	neutral	None	None	None	None	N
L/N	0.9166	likely_pathogenic	0.9179	pathogenic	-2.99	Highly Destabilizing	0.497	N	0.79	deleterious	None	None	None	None	N
L/P	0.9665	likely_pathogenic	0.9652	pathogenic	-1.751	Destabilizing	0.822	D	0.795	deleterious	D	0.534697127	None	None	N
L/Q	0.7773	likely_pathogenic	0.7924	pathogenic	-2.782	Highly Destabilizing	0.497	N	0.781	deleterious	None	None	None	None	N
L/R	0.8159	likely_pathogenic	0.8224	pathogenic	-2.25	Highly Destabilizing	0.096	N	0.763	deleterious	D	0.534697127	None	None	N
L/S	0.8614	likely_pathogenic	0.8741	pathogenic	-3.697	Highly Destabilizing	0.22	N	0.697	prob.neutral	None	None	None	None	N
L/T	0.7364	likely_pathogenic	0.7541	pathogenic	-3.27	Highly Destabilizing	0.22	N	0.606	neutral	None	None	None	None	N
L/V	0.0896	likely_benign	0.0902	benign	-1.751	Destabilizing	None	N	0.317	neutral	N	0.453731969	None	None	N
L/W	0.5999	likely_pathogenic	0.6113	pathogenic	-2.276	Highly Destabilizing	0.958	D	0.807	deleterious	None	None	None	None	N
L/Y	0.6534	likely_pathogenic	0.6472	pathogenic	-2.022	Highly Destabilizing	0.497	N	0.721	prob.delet.	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.