TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9322	28189;28190;28191	chr2:178711272;178711271;178711270	chr2:179575999;179575998;179575997
N2AB	9005	27238;27239;27240	chr2:178711272;178711271;178711270	chr2:179575999;179575998;179575997
N2A	8078	24457;24458;24459	chr2:178711272;178711271;178711270	chr2:179575999;179575998;179575997
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: C
• RefSeq wild type transcript codon: TGT
• RefSeq wild type template codon: ACA
• Domain: Ig-79
• Domain position: 22
• Structural Position: 33
• Q(SASA): 0.0913
• Site annotation: disulfide
• 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
C/S	None	None	1.0	None	0.827	0.701	0.725725988762	gnomAD-4.0.0	1.592E-06	None	None	disulfide	None	N	None	0	0	None	0	0	None	0	0	2.85889E-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
C/A	0.696	likely_pathogenic	0.6909	pathogenic	-1.693	Destabilizing	0.998	D	0.729	prob.delet.	None	None	disulfide	None	N
C/D	0.9966	likely_pathogenic	0.9967	pathogenic	-1.577	Destabilizing	1.0	D	0.917	deleterious	None	None	disulfide	None	N
C/E	0.998	likely_pathogenic	0.9982	pathogenic	-1.364	Destabilizing	1.0	D	0.929	deleterious	None	None	disulfide	None	N
C/F	0.8177	likely_pathogenic	0.8309	pathogenic	-1.17	Destabilizing	1.0	D	0.918	deleterious	None	None	disulfide	None	N
C/G	0.6131	likely_pathogenic	0.5868	pathogenic	-2.032	Highly Destabilizing	1.0	D	0.907	deleterious	None	None	disulfide	None	N
C/H	0.9901	likely_pathogenic	0.9919	pathogenic	-2.303	Highly Destabilizing	1.0	D	0.923	deleterious	None	None	disulfide	None	N
C/I	0.8157	likely_pathogenic	0.7946	pathogenic	-0.785	Destabilizing	1.0	D	0.85	deleterious	None	None	disulfide	None	N
C/K	0.9986	likely_pathogenic	0.9989	pathogenic	-1.152	Destabilizing	1.0	D	0.917	deleterious	None	None	disulfide	None	N
C/L	0.825	likely_pathogenic	0.8109	pathogenic	-0.785	Destabilizing	0.999	D	0.777	deleterious	None	None	disulfide	None	N
C/M	0.915	likely_pathogenic	0.9007	pathogenic	-0.149	Destabilizing	1.0	D	0.883	deleterious	None	None	disulfide	None	N
C/N	0.9821	likely_pathogenic	0.9833	pathogenic	-1.645	Destabilizing	1.0	D	0.927	deleterious	None	None	disulfide	None	N
C/P	0.9983	likely_pathogenic	0.9985	pathogenic	-1.065	Destabilizing	1.0	D	0.929	deleterious	None	None	disulfide	None	N
C/Q	0.9935	likely_pathogenic	0.9946	pathogenic	-1.274	Destabilizing	1.0	D	0.943	deleterious	None	None	disulfide	None	N
C/R	0.9859	likely_pathogenic	0.9893	pathogenic	-1.477	Destabilizing	1.0	D	0.933	deleterious	None	None	disulfide	None	N
C/S	0.7471	likely_pathogenic	0.7262	pathogenic	-1.963	Destabilizing	1.0	D	0.827	deleterious	None	None	disulfide	None	N
C/T	0.8088	likely_pathogenic	0.7829	pathogenic	-1.569	Destabilizing	1.0	D	0.832	deleterious	None	None	disulfide	None	N
C/V	0.6791	likely_pathogenic	0.65	pathogenic	-1.065	Destabilizing	0.999	D	0.797	deleterious	None	None	disulfide	None	N
C/W	0.9856	likely_pathogenic	0.9885	pathogenic	-1.537	Destabilizing	1.0	D	0.906	deleterious	None	None	disulfide	None	N
C/Y	0.9613	likely_pathogenic	0.9689	pathogenic	-1.317	Destabilizing	1.0	D	0.931	deleterious	None	None	disulfide	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.