TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31125	93598;93599;93600	chr2:178548253;178548252;178548251	chr2:179412980;179412979;179412978
N2AB	29484	88675;88676;88677	chr2:178548253;178548252;178548251	chr2:179412980;179412979;179412978
N2A	28557	85894;85895;85896	chr2:178548253;178548252;178548251	chr2:179412980;179412979;179412978
N2B	22060	66403;66404;66405	chr2:178548253;178548252;178548251	chr2:179412980;179412979;179412978
Novex-1	22185	66778;66779;66780	chr2:178548253;178548252;178548251	chr2:179412980;179412979;179412978
Novex-2	22252	66979;66980;66981	chr2:178548253;178548252;178548251	chr2:179412980;179412979;179412978
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Fn3-115
• Domain position: 13
• Structural Position: 15
• Q(SASA): 0.3674
• 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
T/S	None	None	0.999	N	0.471	0.361	0.299770980665	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-06	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
T/A	0.1648	likely_benign	0.1541	benign	-1.101	Destabilizing	0.999	D	0.492	neutral	N	0.439788732	None	None	N
T/C	0.5066	ambiguous	0.5135	ambiguous	-0.982	Destabilizing	1.0	D	0.709	prob.delet.	None	None	None	None	N
T/D	0.8703	likely_pathogenic	0.8257	pathogenic	-0.989	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
T/E	0.8048	likely_pathogenic	0.7274	pathogenic	-0.95	Destabilizing	1.0	D	0.763	deleterious	None	None	None	None	N
T/F	0.6084	likely_pathogenic	0.5346	ambiguous	-1.275	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
T/G	0.5858	likely_pathogenic	0.5457	ambiguous	-1.355	Destabilizing	1.0	D	0.707	prob.neutral	None	None	None	None	N
T/H	0.6522	likely_pathogenic	0.5897	pathogenic	-1.661	Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	N
T/I	0.2399	likely_benign	0.2049	benign	-0.5	Destabilizing	1.0	D	0.765	deleterious	N	0.38456738	None	None	N
T/K	0.678	likely_pathogenic	0.5663	pathogenic	-0.778	Destabilizing	1.0	D	0.767	deleterious	None	None	None	None	N
T/L	0.2161	likely_benign	0.1872	benign	-0.5	Destabilizing	0.999	D	0.675	prob.neutral	None	None	None	None	N
T/M	0.1629	likely_benign	0.1503	benign	-0.195	Destabilizing	1.0	D	0.712	prob.delet.	None	None	None	None	N
T/N	0.4329	ambiguous	0.3928	ambiguous	-0.932	Destabilizing	1.0	D	0.681	prob.neutral	N	0.501914626	None	None	N
T/P	0.5002	ambiguous	0.4398	ambiguous	-0.671	Destabilizing	1.0	D	0.763	deleterious	N	0.48132871	None	None	N
T/Q	0.6308	likely_pathogenic	0.5465	ambiguous	-1.154	Destabilizing	1.0	D	0.776	deleterious	None	None	None	None	N
T/R	0.5895	likely_pathogenic	0.4653	ambiguous	-0.576	Destabilizing	1.0	D	0.77	deleterious	None	None	None	None	N
T/S	0.238	likely_benign	0.238	benign	-1.187	Destabilizing	0.999	D	0.471	neutral	N	0.45387275	None	None	N
T/V	0.1705	likely_benign	0.1524	benign	-0.671	Destabilizing	0.999	D	0.557	neutral	None	None	None	None	N
T/W	0.9147	likely_pathogenic	0.8839	pathogenic	-1.196	Destabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	N
T/Y	0.656	likely_pathogenic	0.5827	pathogenic	-0.909	Destabilizing	1.0	D	0.761	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.