TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7116	21571;21572;21573	chr2:178723913;178723912;178723911	chr2:179588640;179588639;179588638
N2AB	6799	20620;20621;20622	chr2:178723913;178723912;178723911	chr2:179588640;179588639;179588638
N2A	5872	17839;17840;17841	chr2:178723913;178723912;178723911	chr2:179588640;179588639;179588638
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: TGC
• RefSeq wild type template codon: ACG
• Domain: Ig-55
• Domain position: 73
• Structural Position: 156
• Q(SASA): 0.0617
• 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/W	rs750661972	-1.64	1.0	D	0.861	0.513	0.468753983522	gnomAD-2.1.1	4.03E-06	None	None	disulfide	None	N	None	0	0	None	0	5.57E-05	None	0	None	0	0	0
C/W	rs750661972	-1.64	1.0	D	0.861	0.513	0.468753983522	gnomAD-4.0.0	6.84374E-07	None	None	disulfide	None	N	None	0	0	None	0	2.52003E-05	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
C/A	0.8633	likely_pathogenic	0.8431	pathogenic	-1.621	Destabilizing	0.998	D	0.719	prob.delet.	None	None	disulfide	None	N
C/D	0.9996	likely_pathogenic	0.9995	pathogenic	-1.727	Destabilizing	1.0	D	0.876	deleterious	None	None	disulfide	None	N
C/E	0.9996	likely_pathogenic	0.9996	pathogenic	-1.49	Destabilizing	1.0	D	0.897	deleterious	None	None	disulfide	None	N
C/F	0.874	likely_pathogenic	0.8451	pathogenic	-0.928	Destabilizing	1.0	D	0.883	deleterious	D	0.572727657	disulfide	None	N
C/G	0.8658	likely_pathogenic	0.8485	pathogenic	-1.96	Destabilizing	1.0	D	0.872	deleterious	D	0.574248594	disulfide	None	N
C/H	0.9982	likely_pathogenic	0.9978	pathogenic	-2.119	Highly Destabilizing	1.0	D	0.892	deleterious	None	None	disulfide	None	N
C/I	0.8863	likely_pathogenic	0.8678	pathogenic	-0.693	Destabilizing	1.0	D	0.809	deleterious	None	None	disulfide	None	N
C/K	0.9997	likely_pathogenic	0.9997	pathogenic	-1.354	Destabilizing	1.0	D	0.875	deleterious	None	None	disulfide	None	N
C/L	0.8238	likely_pathogenic	0.7989	pathogenic	-0.693	Destabilizing	0.999	D	0.768	deleterious	None	None	disulfide	None	N
C/M	0.9558	likely_pathogenic	0.9495	pathogenic	-0.055	Destabilizing	1.0	D	0.828	deleterious	None	None	disulfide	None	N
C/N	0.9979	likely_pathogenic	0.9974	pathogenic	-1.956	Destabilizing	1.0	D	0.897	deleterious	None	None	disulfide	None	N
C/P	0.9989	likely_pathogenic	0.9984	pathogenic	-0.983	Destabilizing	1.0	D	0.896	deleterious	None	None	disulfide	None	N
C/Q	0.9989	likely_pathogenic	0.9986	pathogenic	-1.462	Destabilizing	1.0	D	0.903	deleterious	None	None	disulfide	None	N
C/R	0.9951	likely_pathogenic	0.9942	pathogenic	-1.738	Destabilizing	1.0	D	0.899	deleterious	D	0.562892289	disulfide	None	N
C/S	0.9587	likely_pathogenic	0.9518	pathogenic	-2.235	Highly Destabilizing	1.0	D	0.799	deleterious	D	0.574248594	disulfide	None	N
C/T	0.9742	likely_pathogenic	0.9692	pathogenic	-1.835	Destabilizing	1.0	D	0.811	deleterious	None	None	disulfide	None	N
C/V	0.7571	likely_pathogenic	0.7315	pathogenic	-0.983	Destabilizing	0.999	D	0.791	deleterious	None	None	disulfide	None	N
C/W	0.9929	likely_pathogenic	0.9908	pathogenic	-1.39	Destabilizing	1.0	D	0.861	deleterious	D	0.574248594	disulfide	None	N
C/Y	0.9822	likely_pathogenic	0.9781	pathogenic	-1.189	Destabilizing	1.0	D	0.894	deleterious	D	0.574248594	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.