TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	10010	30253;30254;30255	chr2:178704342;178704341;178704340	chr2:179569069;179569068;179569067
N2AB	9693	29302;29303;29304	chr2:178704342;178704341;178704340	chr2:179569069;179569068;179569067
N2A	8766	26521;26522;26523	chr2:178704342;178704341;178704340	chr2:179569069;179569068;179569067
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-85
• Domain position: 22
• Structural Position: 33
• Q(SASA): 0.0599
• 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/G	None	None	1.0	None	0.91	0.701	0.856695912731	gnomAD-4.0.0	1.59085E-06	None	None	disulfide	None	N	None	0	0	None	0	0	None	0	0	2.85747E-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	0.9389	likely_pathogenic	0.9422	pathogenic	-1.907	Destabilizing	0.998	D	0.663	neutral	None	None	disulfide	None	N
C/D	0.9995	likely_pathogenic	0.9996	pathogenic	-1.751	Destabilizing	1.0	D	0.916	deleterious	None	None	disulfide	None	N
C/E	0.9998	likely_pathogenic	0.9998	pathogenic	-1.548	Destabilizing	1.0	D	0.936	deleterious	None	None	disulfide	None	N
C/F	0.9457	likely_pathogenic	0.954	pathogenic	-1.183	Destabilizing	1.0	D	0.917	deleterious	None	None	disulfide	None	N
C/G	0.8899	likely_pathogenic	0.893	pathogenic	-2.235	Highly Destabilizing	1.0	D	0.91	deleterious	None	None	disulfide	None	N
C/H	0.9984	likely_pathogenic	0.9985	pathogenic	-2.408	Highly Destabilizing	1.0	D	0.929	deleterious	None	None	disulfide	None	N
C/I	0.9683	likely_pathogenic	0.9764	pathogenic	-1.018	Destabilizing	1.0	D	0.857	deleterious	None	None	disulfide	None	N
C/K	0.9998	likely_pathogenic	0.9998	pathogenic	-1.67	Destabilizing	1.0	D	0.916	deleterious	None	None	disulfide	None	N
C/L	0.9566	likely_pathogenic	0.9648	pathogenic	-1.018	Destabilizing	0.999	D	0.766	deleterious	None	None	disulfide	None	N
C/M	0.9849	likely_pathogenic	0.9877	pathogenic	-0.122	Destabilizing	1.0	D	0.884	deleterious	None	None	disulfide	None	N
C/N	0.9979	likely_pathogenic	0.998	pathogenic	-2.063	Highly Destabilizing	1.0	D	0.933	deleterious	None	None	disulfide	None	N
C/P	0.9996	likely_pathogenic	0.9996	pathogenic	-1.294	Destabilizing	1.0	D	0.935	deleterious	None	None	disulfide	None	N
C/Q	0.9993	likely_pathogenic	0.9994	pathogenic	-1.681	Destabilizing	1.0	D	0.948	deleterious	None	None	disulfide	None	N
C/R	0.9975	likely_pathogenic	0.9978	pathogenic	-1.875	Destabilizing	1.0	D	0.939	deleterious	None	None	disulfide	None	N
C/S	0.956	likely_pathogenic	0.9574	pathogenic	-2.412	Highly Destabilizing	1.0	D	0.842	deleterious	None	None	disulfide	None	N
C/T	0.9751	likely_pathogenic	0.9769	pathogenic	-2.049	Highly Destabilizing	1.0	D	0.847	deleterious	None	None	disulfide	None	N
C/V	0.907	likely_pathogenic	0.9271	pathogenic	-1.294	Destabilizing	0.999	D	0.809	deleterious	None	None	disulfide	None	N
C/W	0.996	likely_pathogenic	0.9967	pathogenic	-1.567	Destabilizing	1.0	D	0.917	deleterious	None	None	disulfide	None	N
C/Y	0.9908	likely_pathogenic	0.9922	pathogenic	-1.421	Destabilizing	1.0	D	0.935	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.