TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7450	22573;22574;22575	chr2:178722439;178722438;178722437	chr2:179587166;179587165;179587164
N2AB	7133	21622;21623;21624	chr2:178722439;178722438;178722437	chr2:179587166;179587165;179587164
N2A	6206	18841;18842;18843	chr2:178722439;178722438;178722437	chr2:179587166;179587165;179587164
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: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Ig-59
• Domain position: 32
• Structural Position: 46
• Q(SASA): 0.2559
• 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
V/A	None	None	0.999	D	0.621	0.641	0.782002166855	gnomAD-4.0.0	2.05301E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.69889E-06	0	0
V/L	rs1195511070	-0.468	0.922	D	0.541	0.491	0.670247443365	gnomAD-2.1.1	8.05E-06	None	None	None	None	I	None	0	0	None	0	0	None	6.54E-05	None	0	0	0
V/L	rs1195511070	-0.468	0.922	D	0.541	0.491	0.670247443365	gnomAD-4.0.0	3.1839E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	2.86607E-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
V/A	0.4479	ambiguous	0.4247	ambiguous	-1.435	Destabilizing	0.999	D	0.621	neutral	D	0.563173862	None	None	I
V/C	0.9296	likely_pathogenic	0.9217	pathogenic	-0.952	Destabilizing	1.0	D	0.746	deleterious	None	None	None	None	I
V/D	0.9387	likely_pathogenic	0.93	pathogenic	-1.087	Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	I
V/E	0.8908	likely_pathogenic	0.8734	pathogenic	-1.044	Destabilizing	1.0	D	0.857	deleterious	D	0.634760937	None	None	I
V/F	0.4263	ambiguous	0.409	ambiguous	-1.023	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	I
V/G	0.6284	likely_pathogenic	0.6024	pathogenic	-1.798	Destabilizing	1.0	D	0.858	deleterious	D	0.634760937	None	None	I
V/H	0.9578	likely_pathogenic	0.9482	pathogenic	-1.329	Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	I
V/I	0.0851	likely_benign	0.0909	benign	-0.524	Destabilizing	0.503	D	0.202	neutral	None	None	None	None	I
V/K	0.934	likely_pathogenic	0.9197	pathogenic	-1.09	Destabilizing	1.0	D	0.86	deleterious	None	None	None	None	I
V/L	0.367	ambiguous	0.3897	ambiguous	-0.524	Destabilizing	0.922	D	0.541	neutral	D	0.554826653	None	None	I
V/M	0.3643	ambiguous	0.3529	ambiguous	-0.475	Destabilizing	1.0	D	0.711	prob.delet.	D	0.602086442	None	None	I
V/N	0.8456	likely_pathogenic	0.8293	pathogenic	-0.914	Destabilizing	0.999	D	0.874	deleterious	None	None	None	None	I
V/P	0.8434	likely_pathogenic	0.8654	pathogenic	-0.793	Destabilizing	0.999	D	0.857	deleterious	None	None	None	None	I
V/Q	0.9065	likely_pathogenic	0.889	pathogenic	-0.997	Destabilizing	1.0	D	0.874	deleterious	None	None	None	None	I
V/R	0.9007	likely_pathogenic	0.8831	pathogenic	-0.699	Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	I
V/S	0.683	likely_pathogenic	0.6546	pathogenic	-1.487	Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	I
V/T	0.4622	ambiguous	0.4308	ambiguous	-1.314	Destabilizing	0.997	D	0.712	prob.delet.	None	None	None	None	I
V/W	0.9688	likely_pathogenic	0.9656	pathogenic	-1.236	Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	I
V/Y	0.8775	likely_pathogenic	0.8585	pathogenic	-0.918	Destabilizing	1.0	D	0.765	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.