TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28715	86368;86369;86370	chr2:178559989;178559988;178559987	chr2:179424716;179424715;179424714
N2AB	27074	81445;81446;81447	chr2:178559989;178559988;178559987	chr2:179424716;179424715;179424714
N2A	26147	78664;78665;78666	chr2:178559989;178559988;178559987	chr2:179424716;179424715;179424714
N2B	19650	59173;59174;59175	chr2:178559989;178559988;178559987	chr2:179424716;179424715;179424714
Novex-1	19775	59548;59549;59550	chr2:178559989;178559988;178559987	chr2:179424716;179424715;179424714
Novex-2	19842	59749;59750;59751	chr2:178559989;178559988;178559987	chr2:179424716;179424715;179424714
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTA
• RefSeq wild type template codon: GAT
• Domain: Fn3-97
• Domain position: 65
• Structural Position: 97
• Q(SASA): 0.1073
• 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/P	rs1423594263	-1.83	0.998	D	0.887	0.893	0.921956819008	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
L/P	rs1423594263	-1.83	0.998	D	0.887	0.893	0.921956819008	gnomAD-4.0.0	1.59135E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43275E-05	0
L/R	None	None	0.142	D	0.754	0.888	0.900562439436	gnomAD-4.0.0	1.59135E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43275E-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
L/A	0.9357	likely_pathogenic	0.9359	pathogenic	-2.496	Highly Destabilizing	0.968	D	0.805	deleterious	None	None	None	None	N
L/C	0.8946	likely_pathogenic	0.905	pathogenic	-2.363	Highly Destabilizing	1.0	D	0.812	deleterious	None	None	None	None	N
L/D	0.9986	likely_pathogenic	0.9982	pathogenic	-1.689	Destabilizing	0.995	D	0.881	deleterious	None	None	None	None	N
L/E	0.9923	likely_pathogenic	0.9901	pathogenic	-1.536	Destabilizing	0.991	D	0.866	deleterious	None	None	None	None	N
L/F	0.639	likely_pathogenic	0.7152	pathogenic	-1.773	Destabilizing	0.998	D	0.87	deleterious	None	None	None	None	N
L/G	0.986	likely_pathogenic	0.9853	pathogenic	-2.97	Highly Destabilizing	0.991	D	0.874	deleterious	None	None	None	None	N
L/H	0.9806	likely_pathogenic	0.9794	pathogenic	-2.127	Highly Destabilizing	0.999	D	0.875	deleterious	None	None	None	None	N
L/I	0.2674	likely_benign	0.2608	benign	-1.167	Destabilizing	0.979	D	0.821	deleterious	D	0.608015539	None	None	N
L/K	0.9815	likely_pathogenic	0.9777	pathogenic	-1.728	Destabilizing	0.982	D	0.846	deleterious	None	None	None	None	N
L/M	0.3473	ambiguous	0.3829	ambiguous	-1.285	Destabilizing	0.998	D	0.841	deleterious	None	None	None	None	N
L/N	0.9881	likely_pathogenic	0.9853	pathogenic	-1.861	Destabilizing	0.991	D	0.878	deleterious	None	None	None	None	N
L/P	0.9867	likely_pathogenic	0.9845	pathogenic	-1.587	Destabilizing	0.998	D	0.887	deleterious	D	0.660908001	None	None	N
L/Q	0.966	likely_pathogenic	0.9591	pathogenic	-1.837	Destabilizing	0.988	D	0.869	deleterious	D	0.623529492	None	None	N
L/R	0.9698	likely_pathogenic	0.9629	pathogenic	-1.327	Destabilizing	0.142	N	0.754	deleterious	D	0.660908001	None	None	N
L/S	0.9898	likely_pathogenic	0.9882	pathogenic	-2.771	Highly Destabilizing	0.991	D	0.861	deleterious	None	None	None	None	N
L/T	0.957	likely_pathogenic	0.9521	pathogenic	-2.458	Highly Destabilizing	0.991	D	0.834	deleterious	None	None	None	None	N
L/V	0.3428	ambiguous	0.3348	benign	-1.587	Destabilizing	0.979	D	0.832	deleterious	D	0.580962998	None	None	N
L/W	0.9564	likely_pathogenic	0.9683	pathogenic	-1.827	Destabilizing	1.0	D	0.81	deleterious	None	None	None	None	N
L/Y	0.966	likely_pathogenic	0.9713	pathogenic	-1.617	Destabilizing	0.998	D	0.838	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.