TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2244	6955;6956;6957	chr2:178774981;178774980;178774979	chr2:179639708;179639707;179639706
N2AB	2244	6955;6956;6957	chr2:178774981;178774980;178774979	chr2:179639708;179639707;179639706
N2A	2244	6955;6956;6957	chr2:178774981;178774980;178774979	chr2:179639708;179639707;179639706
N2B	2198	6817;6818;6819	chr2:178774981;178774980;178774979	chr2:179639708;179639707;179639706
Novex-1	2198	6817;6818;6819	chr2:178774981;178774980;178774979	chr2:179639708;179639707;179639706
Novex-2	2198	6817;6818;6819	chr2:178774981;178774980;178774979	chr2:179639708;179639707;179639706
Novex-3	2244	6955;6956;6957	chr2:178774981;178774980;178774979	chr2:179639708;179639707;179639706

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAC
• RefSeq wild type template codon: ATG
• Domain: Ig-11
• Domain position: 71
• Structural Position: 154
• Q(SASA): 0.0934
• 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/C	None	None	1.0	D	0.869	0.426	0.427713192076	gnomAD-4.0.0	8.40229E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.18756E-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	0.9886	likely_pathogenic	0.9899	pathogenic	-2.7	Highly Destabilizing	0.998	D	0.841	deleterious	None	None	None	None	N
Y/C	0.8495	likely_pathogenic	0.8626	pathogenic	-1.567	Destabilizing	1.0	D	0.869	deleterious	D	0.632902824	None	None	N
Y/D	0.9956	likely_pathogenic	0.996	pathogenic	-3.473	Highly Destabilizing	1.0	D	0.885	deleterious	D	0.632902824	None	None	N
Y/E	0.9981	likely_pathogenic	0.9983	pathogenic	-3.23	Highly Destabilizing	1.0	D	0.887	deleterious	None	None	None	None	N
Y/F	0.0905	likely_benign	0.0975	benign	-1.092	Destabilizing	0.434	N	0.413	neutral	N	0.509040805	None	None	N
Y/G	0.9882	likely_pathogenic	0.9888	pathogenic	-3.142	Highly Destabilizing	1.0	D	0.887	deleterious	None	None	None	None	N
Y/H	0.9356	likely_pathogenic	0.9411	pathogenic	-2.414	Highly Destabilizing	1.0	D	0.737	prob.delet.	D	0.632902824	None	None	N
Y/I	0.7536	likely_pathogenic	0.7781	pathogenic	-1.218	Destabilizing	0.999	D	0.808	deleterious	None	None	None	None	N
Y/K	0.9967	likely_pathogenic	0.997	pathogenic	-2.2	Highly Destabilizing	1.0	D	0.887	deleterious	None	None	None	None	N
Y/L	0.765	likely_pathogenic	0.779	pathogenic	-1.218	Destabilizing	0.994	D	0.766	deleterious	None	None	None	None	N
Y/M	0.9392	likely_pathogenic	0.9463	pathogenic	-1.097	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
Y/N	0.9727	likely_pathogenic	0.9748	pathogenic	-3.177	Highly Destabilizing	1.0	D	0.878	deleterious	D	0.632902824	None	None	N
Y/P	0.9983	likely_pathogenic	0.9983	pathogenic	-1.731	Destabilizing	1.0	D	0.895	deleterious	None	None	None	None	N
Y/Q	0.9969	likely_pathogenic	0.9971	pathogenic	-2.749	Highly Destabilizing	1.0	D	0.808	deleterious	None	None	None	None	N
Y/R	0.988	likely_pathogenic	0.9889	pathogenic	-2.382	Highly Destabilizing	1.0	D	0.872	deleterious	None	None	None	None	N
Y/S	0.9745	likely_pathogenic	0.9766	pathogenic	-3.392	Highly Destabilizing	1.0	D	0.878	deleterious	D	0.632902824	None	None	N
Y/T	0.9813	likely_pathogenic	0.9835	pathogenic	-3.005	Highly Destabilizing	1.0	D	0.883	deleterious	None	None	None	None	N
Y/V	0.7224	likely_pathogenic	0.746	pathogenic	-1.731	Destabilizing	0.997	D	0.789	deleterious	None	None	None	None	N
Y/W	0.8042	likely_pathogenic	0.8125	pathogenic	-0.452	Destabilizing	1.0	D	0.727	prob.delet.	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.