TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8900	26923;26924;26925	chr2:178713960;178713959;178713958	chr2:179578687;179578686;179578685
N2AB	8583	25972;25973;25974	chr2:178713960;178713959;178713958	chr2:179578687;179578686;179578685
N2A	7656	23191;23192;23193	chr2:178713960;178713959;178713958	chr2:179578687;179578686;179578685
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: Y
• RefSeq wild type transcript codon: TAC
• RefSeq wild type template codon: ATG
• Domain: Ig-74
• Domain position: 71
• Structural Position: 154
• Q(SASA): 0.107
• 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
Y/D	None	None	1.0	D	0.893	0.838	0.924701767363	gnomAD-4.0.0	8.41302E-06	None	None	None	None	N	None	6.34437E-05	0	None	0	0	None	0	0	7.88469E-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
Y/A	0.9882	likely_pathogenic	0.9916	pathogenic	-2.403	Highly Destabilizing	1.0	D	0.868	deleterious	None	None	None	None	N
Y/C	0.7621	likely_pathogenic	0.8366	pathogenic	-1.794	Destabilizing	1.0	D	0.875	deleterious	D	0.659227512	None	None	N
Y/D	0.9962	likely_pathogenic	0.9971	pathogenic	-2.94	Highly Destabilizing	1.0	D	0.893	deleterious	D	0.659227512	None	None	N
Y/E	0.9981	likely_pathogenic	0.9985	pathogenic	-2.69	Highly Destabilizing	1.0	D	0.901	deleterious	None	None	None	None	N
Y/F	0.1116	likely_benign	0.1493	benign	-0.822	Destabilizing	0.999	D	0.687	prob.neutral	D	0.588751257	None	None	N
Y/G	0.9855	likely_pathogenic	0.9894	pathogenic	-2.866	Highly Destabilizing	1.0	D	0.901	deleterious	None	None	None	None	N
Y/H	0.9312	likely_pathogenic	0.9526	pathogenic	-2.084	Highly Destabilizing	1.0	D	0.802	deleterious	D	0.643006347	None	None	N
Y/I	0.7339	likely_pathogenic	0.7954	pathogenic	-0.87	Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
Y/K	0.9978	likely_pathogenic	0.9981	pathogenic	-1.949	Destabilizing	1.0	D	0.897	deleterious	None	None	None	None	N
Y/L	0.6942	likely_pathogenic	0.7406	pathogenic	-0.87	Destabilizing	0.999	D	0.797	deleterious	None	None	None	None	N
Y/M	0.9335	likely_pathogenic	0.9561	pathogenic	-0.97	Destabilizing	1.0	D	0.842	deleterious	None	None	None	None	N
Y/N	0.9727	likely_pathogenic	0.9798	pathogenic	-2.866	Highly Destabilizing	1.0	D	0.895	deleterious	D	0.659227512	None	None	N
Y/P	0.9962	likely_pathogenic	0.9971	pathogenic	-1.397	Destabilizing	1.0	D	0.913	deleterious	None	None	None	None	N
Y/Q	0.996	likely_pathogenic	0.9972	pathogenic	-2.426	Highly Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
Y/R	0.9891	likely_pathogenic	0.9906	pathogenic	-2.166	Highly Destabilizing	1.0	D	0.897	deleterious	None	None	None	None	N
Y/S	0.9708	likely_pathogenic	0.9784	pathogenic	-3.225	Highly Destabilizing	1.0	D	0.9	deleterious	D	0.659227512	None	None	N
Y/T	0.9851	likely_pathogenic	0.9895	pathogenic	-2.824	Highly Destabilizing	1.0	D	0.901	deleterious	None	None	None	None	N
Y/V	0.712	likely_pathogenic	0.7747	pathogenic	-1.397	Destabilizing	1.0	D	0.834	deleterious	None	None	None	None	N
Y/W	0.6594	likely_pathogenic	0.7311	pathogenic	-0.165	Destabilizing	1.0	D	0.794	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.