TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8006	24241;24242;24243	chr2:178719374;178719373;178719372	chr2:179584101;179584100;179584099
N2AB	7689	23290;23291;23292	chr2:178719374;178719373;178719372	chr2:179584101;179584100;179584099
N2A	6762	20509;20510;20511	chr2:178719374;178719373;178719372	chr2:179584101;179584100;179584099
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-65
• Domain position: 22
• Structural Position: 33
• Q(SASA): 0.097
• 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	rs764282358	-1.784	1.0	D	0.92	0.613	0.795667397281	gnomAD-2.1.1	4.02E-06	None	None	disulfide	None	N	None	0	0	None	0	0	None	0	None	0	8.88E-06	0
C/Y	rs764282358	-1.784	1.0	D	0.92	0.613	0.795667397281	gnomAD-4.0.0	8.89474E-06	None	None	disulfide	None	N	None	0	0	None	0	0	None	0	0	1.16933E-05	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	0.8144	likely_pathogenic	0.8919	pathogenic	-1.717	Destabilizing	0.998	D	0.723	prob.delet.	None	None	disulfide	None	N
C/D	0.996	likely_pathogenic	0.9981	pathogenic	-1.81	Destabilizing	1.0	D	0.907	deleterious	None	None	disulfide	None	N
C/E	0.9979	likely_pathogenic	0.999	pathogenic	-1.583	Destabilizing	1.0	D	0.917	deleterious	None	None	disulfide	None	N
C/F	0.8556	likely_pathogenic	0.9186	pathogenic	-1.053	Destabilizing	1.0	D	0.908	deleterious	D	0.549735103	disulfide	None	N
C/G	0.5341	ambiguous	0.7093	pathogenic	-2.052	Highly Destabilizing	1.0	D	0.899	deleterious	D	0.523237057	disulfide	None	N
C/H	0.9929	likely_pathogenic	0.9965	pathogenic	-2.253	Highly Destabilizing	1.0	D	0.911	deleterious	None	None	disulfide	None	N
C/I	0.8581	likely_pathogenic	0.9305	pathogenic	-0.807	Destabilizing	1.0	D	0.841	deleterious	None	None	disulfide	None	N
C/K	0.9989	likely_pathogenic	0.9994	pathogenic	-1.532	Destabilizing	1.0	D	0.907	deleterious	None	None	disulfide	None	N
C/L	0.8446	likely_pathogenic	0.9195	pathogenic	-0.807	Destabilizing	0.999	D	0.76	deleterious	None	None	disulfide	None	N
C/M	0.9176	likely_pathogenic	0.9587	pathogenic	-0.268	Destabilizing	1.0	D	0.869	deleterious	None	None	disulfide	None	N
C/N	0.9794	likely_pathogenic	0.9907	pathogenic	-2.063	Highly Destabilizing	1.0	D	0.915	deleterious	None	None	disulfide	None	N
C/P	0.998	likely_pathogenic	0.999	pathogenic	-1.09	Destabilizing	1.0	D	0.917	deleterious	None	None	disulfide	None	N
C/Q	0.995	likely_pathogenic	0.9978	pathogenic	-1.611	Destabilizing	1.0	D	0.929	deleterious	None	None	disulfide	None	N
C/R	0.992	likely_pathogenic	0.9955	pathogenic	-1.829	Destabilizing	1.0	D	0.919	deleterious	D	0.549988593	disulfide	None	N
C/S	0.8204	likely_pathogenic	0.9216	pathogenic	-2.357	Highly Destabilizing	1.0	D	0.811	deleterious	D	0.527022492	disulfide	None	N
C/T	0.8739	likely_pathogenic	0.9487	pathogenic	-1.965	Destabilizing	1.0	D	0.817	deleterious	None	None	disulfide	None	N
C/V	0.7394	likely_pathogenic	0.8444	pathogenic	-1.09	Destabilizing	0.999	D	0.781	deleterious	None	None	disulfide	None	N
C/W	0.9822	likely_pathogenic	0.9914	pathogenic	-1.5	Destabilizing	1.0	D	0.891	deleterious	D	0.561344898	disulfide	None	N
C/Y	0.9456	likely_pathogenic	0.971	pathogenic	-1.292	Destabilizing	1.0	D	0.92	deleterious	D	0.549735103	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.