TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27940	84043;84044;84045	chr2:178562314;178562313;178562312	chr2:179427041;179427040;179427039
N2AB	26299	79120;79121;79122	chr2:178562314;178562313;178562312	chr2:179427041;179427040;179427039
N2A	25372	76339;76340;76341	chr2:178562314;178562313;178562312	chr2:179427041;179427040;179427039
N2B	18875	56848;56849;56850	chr2:178562314;178562313;178562312	chr2:179427041;179427040;179427039
Novex-1	19000	57223;57224;57225	chr2:178562314;178562313;178562312	chr2:179427041;179427040;179427039
Novex-2	19067	57424;57425;57426	chr2:178562314;178562313;178562312	chr2:179427041;179427040;179427039
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAC
• RefSeq wild type template codon: TTG
• Domain: Fn3-91
• Domain position: 78
• Structural Position: 112
• Q(SASA): 0.0985
• 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
N/D	None	None	0.999	D	0.618	0.567	0.392855499163	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	6.07533E-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
N/A	0.9908	likely_pathogenic	0.9955	pathogenic	-0.384	Destabilizing	1.0	D	0.784	deleterious	None	None	None	None	N
N/C	0.937	likely_pathogenic	0.9583	pathogenic	-0.415	Destabilizing	1.0	D	0.749	deleterious	None	None	None	None	N
N/D	0.983	likely_pathogenic	0.9899	pathogenic	-2.246	Highly Destabilizing	0.999	D	0.618	neutral	D	0.531929882	None	None	N
N/E	0.9971	likely_pathogenic	0.9981	pathogenic	-2.081	Highly Destabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	N
N/F	0.9988	likely_pathogenic	0.9992	pathogenic	-0.342	Destabilizing	1.0	D	0.788	deleterious	None	None	None	None	N
N/G	0.9728	likely_pathogenic	0.9838	pathogenic	-0.694	Destabilizing	1.0	D	0.566	neutral	None	None	None	None	N
N/H	0.9682	likely_pathogenic	0.9783	pathogenic	-0.517	Destabilizing	1.0	D	0.783	deleterious	D	0.559441886	None	None	N
N/I	0.9908	likely_pathogenic	0.9956	pathogenic	0.397	Stabilizing	1.0	D	0.753	deleterious	D	0.54859256	None	None	N
N/K	0.9973	likely_pathogenic	0.9984	pathogenic	-0.123	Destabilizing	1.0	D	0.767	deleterious	D	0.535804223	None	None	N
N/L	0.9702	likely_pathogenic	0.9796	pathogenic	0.397	Stabilizing	1.0	D	0.772	deleterious	None	None	None	None	N
N/M	0.9895	likely_pathogenic	0.9937	pathogenic	0.564	Stabilizing	1.0	D	0.787	deleterious	None	None	None	None	N
N/P	0.9957	likely_pathogenic	0.997	pathogenic	0.165	Stabilizing	1.0	D	0.763	deleterious	None	None	None	None	N
N/Q	0.9969	likely_pathogenic	0.9981	pathogenic	-1.048	Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	N
N/R	0.9948	likely_pathogenic	0.9963	pathogenic	-0.157	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
N/S	0.676	likely_pathogenic	0.7919	pathogenic	-0.925	Destabilizing	1.0	D	0.595	neutral	N	0.509315722	None	None	N
N/T	0.9223	likely_pathogenic	0.9562	pathogenic	-0.612	Destabilizing	1.0	D	0.733	prob.delet.	N	0.512337008	None	None	N
N/V	0.9874	likely_pathogenic	0.9937	pathogenic	0.165	Stabilizing	1.0	D	0.775	deleterious	None	None	None	None	N
N/W	0.9995	likely_pathogenic	0.9997	pathogenic	-0.424	Destabilizing	1.0	D	0.755	deleterious	None	None	None	None	N
N/Y	0.9896	likely_pathogenic	0.9932	pathogenic	0.063	Stabilizing	1.0	D	0.771	deleterious	D	0.541591121	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.