TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6607	20044;20045;20046	chr2:178727759;178727758;178727757	chr2:179592486;179592485;179592484
N2AB	6290	19093;19094;19095	chr2:178727759;178727758;178727757	chr2:179592486;179592485;179592484
N2A	5363	16312;16313;16314	chr2:178727759;178727758;178727757	chr2:179592486;179592485;179592484
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: W
• RefSeq wild type transcript codon: TGG
• RefSeq wild type template codon: ACC
• Domain: Ig-50
• Domain position: 34
• Structural Position: 48
• Q(SASA): 0.1249
• 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
W/R	None	None	1.0	D	0.871	0.919	0.939463572141	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
W/A	0.9824	likely_pathogenic	0.9857	pathogenic	-3.037	Highly Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
W/C	0.9896	likely_pathogenic	0.9926	pathogenic	-1.363	Destabilizing	1.0	D	0.805	deleterious	D	0.703761946	None	None	N
W/D	0.9982	likely_pathogenic	0.998	pathogenic	-3.447	Highly Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
W/E	0.998	likely_pathogenic	0.9979	pathogenic	-3.32	Highly Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
W/F	0.6016	likely_pathogenic	0.6358	pathogenic	-1.963	Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
W/G	0.9459	likely_pathogenic	0.95	pathogenic	-3.28	Highly Destabilizing	1.0	D	0.821	deleterious	D	0.703560142	None	None	N
W/H	0.9888	likely_pathogenic	0.9906	pathogenic	-2.488	Highly Destabilizing	1.0	D	0.834	deleterious	None	None	None	None	N
W/I	0.9221	likely_pathogenic	0.9376	pathogenic	-2.099	Highly Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
W/K	0.9992	likely_pathogenic	0.9992	pathogenic	-2.377	Highly Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
W/L	0.8687	likely_pathogenic	0.8954	pathogenic	-2.099	Highly Destabilizing	1.0	D	0.821	deleterious	D	0.703560142	None	None	N
W/M	0.9672	likely_pathogenic	0.976	pathogenic	-1.461	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
W/N	0.9959	likely_pathogenic	0.9962	pathogenic	-3.112	Highly Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	N
W/P	0.9973	likely_pathogenic	0.9977	pathogenic	-2.443	Highly Destabilizing	1.0	D	0.884	deleterious	None	None	None	None	N
W/Q	0.9987	likely_pathogenic	0.9987	pathogenic	-2.907	Highly Destabilizing	1.0	D	0.854	deleterious	None	None	None	None	N
W/R	0.9982	likely_pathogenic	0.998	pathogenic	-2.25	Highly Destabilizing	1.0	D	0.871	deleterious	D	0.703761946	None	None	N
W/S	0.9777	likely_pathogenic	0.9796	pathogenic	-3.199	Highly Destabilizing	1.0	D	0.85	deleterious	D	0.703761946	None	None	N
W/T	0.9833	likely_pathogenic	0.9862	pathogenic	-2.993	Highly Destabilizing	1.0	D	0.826	deleterious	None	None	None	None	N
W/V	0.9307	likely_pathogenic	0.9474	pathogenic	-2.443	Highly Destabilizing	1.0	D	0.846	deleterious	None	None	None	None	N
W/Y	0.7747	likely_pathogenic	0.7891	pathogenic	-1.798	Destabilizing	1.0	D	0.808	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.