TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5240	15943;15944;15945	chr2:178733671;178733670;178733669	chr2:179598398;179598397;179598396
N2AB	4923	14992;14993;14994	chr2:178733671;178733670;178733669	chr2:179598398;179598397;179598396
N2A	3996	12211;12212;12213	chr2:178733671;178733670;178733669	chr2:179598398;179598397;179598396
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-35
• Domain position: 73
• Structural Position: 156
• Q(SASA): 0.0756
• 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	D	0.861	0.747	0.905871212908	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
C/A	0.8502	likely_pathogenic	0.8619	pathogenic	-1.892	Destabilizing	0.998	D	0.713	prob.delet.	None	None	None	None	N
C/D	0.9996	likely_pathogenic	0.9996	pathogenic	-1.41	Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	N
C/E	0.9997	likely_pathogenic	0.9997	pathogenic	-1.188	Destabilizing	1.0	D	0.893	deleterious	None	None	None	None	N
C/F	0.6601	likely_pathogenic	0.7345	pathogenic	-1.142	Destabilizing	1.0	D	0.879	deleterious	D	0.82200527	None	None	N
C/G	0.8245	likely_pathogenic	0.8369	pathogenic	-2.256	Highly Destabilizing	1.0	D	0.861	deleterious	D	0.82476445	None	None	N
C/H	0.9971	likely_pathogenic	0.9977	pathogenic	-2.35	Highly Destabilizing	1.0	D	0.893	deleterious	None	None	None	None	N
C/I	0.7421	likely_pathogenic	0.7806	pathogenic	-0.903	Destabilizing	1.0	D	0.794	deleterious	None	None	None	None	N
C/K	0.9997	likely_pathogenic	0.9998	pathogenic	-1.249	Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	N
C/L	0.6216	likely_pathogenic	0.6323	pathogenic	-0.903	Destabilizing	0.999	D	0.763	deleterious	None	None	None	None	N
C/M	0.8937	likely_pathogenic	0.9119	pathogenic	0.073	Stabilizing	1.0	D	0.823	deleterious	None	None	None	None	N
C/N	0.9965	likely_pathogenic	0.9969	pathogenic	-1.736	Destabilizing	1.0	D	0.893	deleterious	None	None	None	None	N
C/P	0.9991	likely_pathogenic	0.9992	pathogenic	-1.211	Destabilizing	1.0	D	0.892	deleterious	None	None	None	None	N
C/Q	0.9983	likely_pathogenic	0.9986	pathogenic	-1.324	Destabilizing	1.0	D	0.903	deleterious	None	None	None	None	N
C/R	0.9957	likely_pathogenic	0.9963	pathogenic	-1.558	Destabilizing	1.0	D	0.899	deleterious	D	0.82476445	None	None	N
C/S	0.9487	likely_pathogenic	0.9536	pathogenic	-2.126	Highly Destabilizing	1.0	D	0.791	deleterious	D	0.82476445	None	None	N
C/T	0.9627	likely_pathogenic	0.9673	pathogenic	-1.715	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
C/V	0.6176	likely_pathogenic	0.6681	pathogenic	-1.211	Destabilizing	0.999	D	0.781	deleterious	None	None	None	None	N
C/W	0.9874	likely_pathogenic	0.9916	pathogenic	-1.444	Destabilizing	1.0	D	0.865	deleterious	D	0.82476445	None	None	N
C/Y	0.9511	likely_pathogenic	0.9652	pathogenic	-1.311	Destabilizing	1.0	D	0.894	deleterious	D	0.82476445	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.