TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9467	28624;28625;28626	chr2:178710698;178710697;178710696	chr2:179575425;179575424;179575423
N2AB	9150	27673;27674;27675	chr2:178710698;178710697;178710696	chr2:179575425;179575424;179575423
N2A	8223	24892;24893;24894	chr2:178710698;178710697;178710696	chr2:179575425;179575424;179575423
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: TAT
• RefSeq wild type template codon: ATA
• Domain: Ig-80
• Domain position: 71
• Structural Position: 154
• Q(SASA): 0.0931
• 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/H	rs2076528608	None	1.0	None	0.777	0.783	0.792123652096	gnomAD-4.0.0	1.36866E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79888E-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	0.9944	likely_pathogenic	0.9977	pathogenic	-2.469	Highly Destabilizing	1.0	D	0.856	deleterious	None	None	None	None	N
Y/C	0.9573	likely_pathogenic	0.9817	pathogenic	-1.719	Destabilizing	1.0	D	0.87	deleterious	None	None	None	None	N
Y/D	0.9973	likely_pathogenic	0.9985	pathogenic	-3.212	Highly Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	N
Y/E	0.9985	likely_pathogenic	0.9992	pathogenic	-2.96	Highly Destabilizing	1.0	D	0.886	deleterious	None	None	None	None	N
Y/F	0.2479	likely_benign	0.3078	benign	-0.896	Destabilizing	0.999	D	0.664	neutral	None	None	None	None	N
Y/G	0.9907	likely_pathogenic	0.9942	pathogenic	-2.932	Highly Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	N
Y/H	0.9783	likely_pathogenic	0.9911	pathogenic	-2.27	Highly Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	N
Y/I	0.8526	likely_pathogenic	0.9271	pathogenic	-0.933	Destabilizing	1.0	D	0.834	deleterious	None	None	None	None	N
Y/K	0.9985	likely_pathogenic	0.9993	pathogenic	-2.056	Highly Destabilizing	1.0	D	0.883	deleterious	None	None	None	None	N
Y/L	0.7994	likely_pathogenic	0.8625	pathogenic	-0.933	Destabilizing	0.999	D	0.768	deleterious	None	None	None	None	N
Y/M	0.9568	likely_pathogenic	0.9785	pathogenic	-0.971	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
Y/N	0.9804	likely_pathogenic	0.9912	pathogenic	-3.025	Highly Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	N
Y/P	0.9988	likely_pathogenic	0.9993	pathogenic	-1.462	Destabilizing	1.0	D	0.899	deleterious	None	None	None	None	N
Y/Q	0.9984	likely_pathogenic	0.9994	pathogenic	-2.57	Highly Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	N
Y/R	0.9954	likely_pathogenic	0.9978	pathogenic	-2.285	Highly Destabilizing	1.0	D	0.883	deleterious	None	None	None	None	N
Y/S	0.9917	likely_pathogenic	0.9964	pathogenic	-3.304	Highly Destabilizing	1.0	D	0.883	deleterious	None	None	None	None	N
Y/T	0.9951	likely_pathogenic	0.998	pathogenic	-2.902	Highly Destabilizing	1.0	D	0.885	deleterious	None	None	None	None	N
Y/V	0.837	likely_pathogenic	0.9188	pathogenic	-1.462	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
Y/W	0.8922	likely_pathogenic	0.9101	pathogenic	-0.282	Destabilizing	1.0	D	0.772	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.