TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1642	5149;5150;5151	chr2:178776940;178776939;178776938	chr2:179641667;179641666;179641665
N2AB	1642	5149;5150;5151	chr2:178776940;178776939;178776938	chr2:179641667;179641666;179641665
N2A	1642	5149;5150;5151	chr2:178776940;178776939;178776938	chr2:179641667;179641666;179641665
N2B	1596	5011;5012;5013	chr2:178776940;178776939;178776938	chr2:179641667;179641666;179641665
Novex-1	1596	5011;5012;5013	chr2:178776940;178776939;178776938	chr2:179641667;179641666;179641665
Novex-2	1596	5011;5012;5013	chr2:178776940;178776939;178776938	chr2:179641667;179641666;179641665
Novex-3	1642	5149;5150;5151	chr2:178776940;178776939;178776938	chr2:179641667;179641666;179641665

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGA
• RefSeq wild type template codon: TCT
• Domain: Ig-7
• Domain position: 87
• Structural Position: 171
• Q(SASA): 0.4462
• 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
R/S	rs943254434	None	1.0	N	0.783	0.416	0.353974658523	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
R/S	rs943254434	None	1.0	N	0.783	0.416	0.353974658523	gnomAD-4.0.0	2.02984E-06	None	None	None	None	I	None	3.49443E-05	0	None	0	0	None	0	0	0	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
R/A	0.9895	likely_pathogenic	0.9798	pathogenic	-0.902	Destabilizing	0.999	D	0.648	neutral	None	None	None	None	I
R/C	0.9508	likely_pathogenic	0.895	pathogenic	-0.698	Destabilizing	1.0	D	0.804	deleterious	None	None	None	None	I
R/D	0.9971	likely_pathogenic	0.9944	pathogenic	-0.079	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	I
R/E	0.9868	likely_pathogenic	0.975	pathogenic	0.063	Stabilizing	0.999	D	0.65	neutral	None	None	None	None	I
R/F	0.9907	likely_pathogenic	0.9839	pathogenic	-0.707	Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	I
R/G	0.9848	likely_pathogenic	0.9679	pathogenic	-1.222	Destabilizing	1.0	D	0.773	deleterious	N	0.502687105	None	None	I
R/H	0.833	likely_pathogenic	0.6994	pathogenic	-1.724	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	I
R/I	0.9738	likely_pathogenic	0.9556	pathogenic	-0.038	Destabilizing	1.0	D	0.788	deleterious	N	0.511113036	None	None	I
R/K	0.756	likely_pathogenic	0.6354	pathogenic	-0.716	Destabilizing	0.997	D	0.499	neutral	N	0.481025746	None	None	I
R/L	0.964	likely_pathogenic	0.9342	pathogenic	-0.038	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	I
R/M	0.9889	likely_pathogenic	0.9749	pathogenic	-0.372	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	I
R/N	0.9952	likely_pathogenic	0.9898	pathogenic	-0.277	Destabilizing	1.0	D	0.768	deleterious	None	None	None	None	I
R/P	0.9959	likely_pathogenic	0.9937	pathogenic	-0.306	Destabilizing	1.0	D	0.792	deleterious	None	None	None	None	I
R/Q	0.8732	likely_pathogenic	0.7619	pathogenic	-0.38	Destabilizing	1.0	D	0.767	deleterious	None	None	None	None	I
R/S	0.9914	likely_pathogenic	0.9819	pathogenic	-1.028	Destabilizing	1.0	D	0.783	deleterious	N	0.479302329	None	None	I
R/T	0.9865	likely_pathogenic	0.971	pathogenic	-0.689	Destabilizing	1.0	D	0.773	deleterious	N	0.491189038	None	None	I
R/V	0.9753	likely_pathogenic	0.9608	pathogenic	-0.306	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	I
R/W	0.9212	likely_pathogenic	0.8652	pathogenic	-0.395	Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	I
R/Y	0.9776	likely_pathogenic	0.9596	pathogenic	-0.12	Destabilizing	1.0	D	0.809	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.