TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6502	19729;19730;19731	chr2:178728320;178728319;178728318	chr2:179593047;179593046;179593045
N2AB	6185	18778;18779;18780	chr2:178728320;178728319;178728318	chr2:179593047;179593046;179593045
N2A	5258	15997;15998;15999	chr2:178728320;178728319;178728318	chr2:179593047;179593046;179593045
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-49
• Domain position: 22
• Structural Position: 33
• Q(SASA): 0.1013
• 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/Y	None	None	1.0	D	0.923	0.624	0.81509260357	gnomAD-4.0.0	1.59346E-06	None	None	disulfide	None	N	None	0	0	None	0	0	None	0	2.41663E-04	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	0.8315	likely_pathogenic	0.8819	pathogenic	-1.712	Destabilizing	0.998	D	0.718	prob.delet.	None	None	disulfide	None	N
C/D	0.9947	likely_pathogenic	0.9971	pathogenic	-1.533	Destabilizing	1.0	D	0.906	deleterious	None	None	disulfide	None	N
C/E	0.9967	likely_pathogenic	0.9981	pathogenic	-1.304	Destabilizing	1.0	D	0.92	deleterious	None	None	disulfide	None	N
C/F	0.6799	likely_pathogenic	0.7139	pathogenic	-1.128	Destabilizing	1.0	D	0.911	deleterious	D	0.559610151	disulfide	None	N
C/G	0.534	ambiguous	0.6574	pathogenic	-2.071	Highly Destabilizing	1.0	D	0.899	deleterious	D	0.533112106	disulfide	None	N
C/H	0.9867	likely_pathogenic	0.9928	pathogenic	-2.319	Highly Destabilizing	1.0	D	0.911	deleterious	None	None	disulfide	None	N
C/I	0.8438	likely_pathogenic	0.8633	pathogenic	-0.741	Destabilizing	1.0	D	0.839	deleterious	None	None	disulfide	None	N
C/K	0.9979	likely_pathogenic	0.9987	pathogenic	-1.186	Destabilizing	1.0	D	0.907	deleterious	None	None	disulfide	None	N
C/L	0.8199	likely_pathogenic	0.8568	pathogenic	-0.741	Destabilizing	0.999	D	0.747	deleterious	None	None	disulfide	None	N
C/M	0.8855	likely_pathogenic	0.9099	pathogenic	0.103	Stabilizing	1.0	D	0.867	deleterious	None	None	disulfide	None	N
C/N	0.9747	likely_pathogenic	0.9866	pathogenic	-1.768	Destabilizing	1.0	D	0.918	deleterious	None	None	disulfide	None	N
C/P	0.9972	likely_pathogenic	0.9984	pathogenic	-1.042	Destabilizing	1.0	D	0.919	deleterious	None	None	disulfide	None	N
C/Q	0.9917	likely_pathogenic	0.9955	pathogenic	-1.321	Destabilizing	1.0	D	0.929	deleterious	None	None	disulfide	None	N
C/R	0.9841	likely_pathogenic	0.9912	pathogenic	-1.557	Destabilizing	1.0	D	0.923	deleterious	D	0.559863641	disulfide	None	N
C/S	0.838	likely_pathogenic	0.9124	pathogenic	-2.079	Highly Destabilizing	1.0	D	0.802	deleterious	D	0.536732957	disulfide	None	N
C/T	0.8867	likely_pathogenic	0.934	pathogenic	-1.661	Destabilizing	1.0	D	0.809	deleterious	None	None	disulfide	None	N
C/V	0.7218	likely_pathogenic	0.7572	pathogenic	-1.042	Destabilizing	0.999	D	0.771	deleterious	None	None	disulfide	None	N
C/W	0.9404	likely_pathogenic	0.9573	pathogenic	-1.513	Destabilizing	1.0	D	0.892	deleterious	D	0.559863641	disulfide	None	N
C/Y	0.8535	likely_pathogenic	0.9018	pathogenic	-1.314	Destabilizing	1.0	D	0.923	deleterious	D	0.548089262	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.