TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28119	84580;84581;84582	chr2:178561777;178561776;178561775	chr2:179426504;179426503;179426502
N2AB	26478	79657;79658;79659	chr2:178561777;178561776;178561775	chr2:179426504;179426503;179426502
N2A	25551	76876;76877;76878	chr2:178561777;178561776;178561775	chr2:179426504;179426503;179426502
N2B	19054	57385;57386;57387	chr2:178561777;178561776;178561775	chr2:179426504;179426503;179426502
Novex-1	19179	57760;57761;57762	chr2:178561777;178561776;178561775	chr2:179426504;179426503;179426502
Novex-2	19246	57961;57962;57963	chr2:178561777;178561776;178561775	chr2:179426504;179426503;179426502
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTG
• RefSeq wild type template codon: GAC
• Domain: Fn3-92
• Domain position: 65
• Structural Position: 97
• Q(SASA): 0.1044
• 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
L/P	rs1461216101	-2.097	1.0	D	0.851	0.814	0.951666208339	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
L/P	rs1461216101	-2.097	1.0	D	0.851	0.814	0.951666208339	gnomAD-4.0.0	1.59173E-06	None	None	None	None	I	None	0	2.28707E-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	0.9609	likely_pathogenic	0.957	pathogenic	-2.682	Highly Destabilizing	0.999	D	0.829	deleterious	None	None	None	None	I
L/C	0.9411	likely_pathogenic	0.9318	pathogenic	-2.678	Highly Destabilizing	1.0	D	0.788	deleterious	None	None	None	None	I
L/D	0.999	likely_pathogenic	0.9988	pathogenic	-2.554	Highly Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	I
L/E	0.9949	likely_pathogenic	0.9936	pathogenic	-2.373	Highly Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	I
L/F	0.862	likely_pathogenic	0.8333	pathogenic	-1.876	Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	I
L/G	0.9876	likely_pathogenic	0.9854	pathogenic	-3.173	Highly Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	I
L/H	0.9867	likely_pathogenic	0.9808	pathogenic	-2.404	Highly Destabilizing	1.0	D	0.808	deleterious	None	None	None	None	I
L/I	0.5076	ambiguous	0.5004	ambiguous	-1.284	Destabilizing	0.999	D	0.837	deleterious	None	None	None	None	I
L/K	0.9888	likely_pathogenic	0.9856	pathogenic	-2.022	Highly Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	I
L/M	0.4891	ambiguous	0.4563	ambiguous	-1.529	Destabilizing	1.0	D	0.846	deleterious	D	0.612042701	None	None	I
L/N	0.9898	likely_pathogenic	0.9862	pathogenic	-2.287	Highly Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	I
L/P	0.9891	likely_pathogenic	0.9876	pathogenic	-1.73	Destabilizing	1.0	D	0.851	deleterious	D	0.669730258	None	None	I
L/Q	0.9788	likely_pathogenic	0.9723	pathogenic	-2.253	Highly Destabilizing	1.0	D	0.855	deleterious	D	0.685749619	None	None	I
L/R	0.9814	likely_pathogenic	0.9764	pathogenic	-1.618	Destabilizing	1.0	D	0.849	deleterious	D	0.685749619	None	None	I
L/S	0.9923	likely_pathogenic	0.9911	pathogenic	-3.115	Highly Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	I
L/T	0.9674	likely_pathogenic	0.9658	pathogenic	-2.781	Highly Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	I
L/V	0.5576	ambiguous	0.5545	ambiguous	-1.73	Destabilizing	0.999	D	0.845	deleterious	D	0.608126262	None	None	I
L/W	0.9849	likely_pathogenic	0.9809	pathogenic	-2.023	Highly Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	I
L/Y	0.984	likely_pathogenic	0.9781	pathogenic	-1.799	Destabilizing	1.0	D	0.825	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.