TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7440	22543;22544;22545	chr2:178722469;178722468;178722467	chr2:179587196;179587195;179587194
N2AB	7123	21592;21593;21594	chr2:178722469;178722468;178722467	chr2:179587196;179587195;179587194
N2A	6196	18811;18812;18813	chr2:178722469;178722468;178722467	chr2:179587196;179587195;179587194
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: TGT
• RefSeq wild type template codon: ACA
• Domain: Ig-59
• Domain position: 22
• Structural Position: 33
• Q(SASA): 0.107
• 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/F	rs2154302041	None	1.0	D	0.913	0.806	0.9316426571	gnomAD-4.0.0	1.20032E-06	None	None	disulfide	None	N	None	0	0	None	0	2.75482E-04	None	0	0	0	0	0
C/Y	None	None	1.0	D	0.927	0.801	0.918509175114	gnomAD-4.0.0	1.20032E-06	None	None	disulfide	None	N	None	0	0	None	0	0	None	0	0	0	6.07533E-05	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	0.7342	likely_pathogenic	0.6747	pathogenic	-1.574	Destabilizing	1.0	D	0.73	prob.delet.	None	None	disulfide	None	N
C/D	0.9977	likely_pathogenic	0.9967	pathogenic	-1.347	Destabilizing	1.0	D	0.914	deleterious	None	None	disulfide	None	N
C/E	0.9988	likely_pathogenic	0.9984	pathogenic	-1.112	Destabilizing	1.0	D	0.927	deleterious	None	None	disulfide	None	N
C/F	0.8392	likely_pathogenic	0.7922	pathogenic	-0.969	Destabilizing	1.0	D	0.913	deleterious	D	0.67480752	disulfide	None	N
C/G	0.5242	ambiguous	0.4463	ambiguous	-1.93	Destabilizing	1.0	D	0.903	deleterious	D	0.659191767	disulfide	None	N
C/H	0.9944	likely_pathogenic	0.9921	pathogenic	-2.153	Highly Destabilizing	1.0	D	0.924	deleterious	None	None	disulfide	None	N
C/I	0.861	likely_pathogenic	0.8225	pathogenic	-0.612	Destabilizing	1.0	D	0.847	deleterious	None	None	disulfide	None	N
C/K	0.9994	likely_pathogenic	0.9992	pathogenic	-0.957	Destabilizing	1.0	D	0.913	deleterious	None	None	disulfide	None	N
C/L	0.843	likely_pathogenic	0.8239	pathogenic	-0.612	Destabilizing	1.0	D	0.777	deleterious	None	None	disulfide	None	N
C/M	0.9359	likely_pathogenic	0.9259	pathogenic	-0.026	Destabilizing	1.0	D	0.88	deleterious	None	None	disulfide	None	N
C/N	0.989	likely_pathogenic	0.9834	pathogenic	-1.525	Destabilizing	1.0	D	0.925	deleterious	None	None	disulfide	None	N
C/P	0.9976	likely_pathogenic	0.9967	pathogenic	-0.91	Destabilizing	1.0	D	0.926	deleterious	None	None	disulfide	None	N
C/Q	0.9962	likely_pathogenic	0.995	pathogenic	-1.06	Destabilizing	1.0	D	0.94	deleterious	None	None	disulfide	None	N
C/R	0.9928	likely_pathogenic	0.9915	pathogenic	-1.403	Destabilizing	1.0	D	0.932	deleterious	D	0.659393572	disulfide	None	N
C/S	0.7665	likely_pathogenic	0.687	pathogenic	-1.829	Destabilizing	1.0	D	0.829	deleterious	D	0.637832619	disulfide	None	N
C/T	0.8549	likely_pathogenic	0.8164	pathogenic	-1.406	Destabilizing	1.0	D	0.835	deleterious	None	None	disulfide	None	N
C/V	0.712	likely_pathogenic	0.6555	pathogenic	-0.91	Destabilizing	1.0	D	0.799	deleterious	None	None	disulfide	None	N
C/W	0.9862	likely_pathogenic	0.9806	pathogenic	-1.359	Destabilizing	1.0	D	0.911	deleterious	D	0.675412933	disulfide	None	N
C/Y	0.9678	likely_pathogenic	0.9558	pathogenic	-1.134	Destabilizing	1.0	D	0.927	deleterious	D	0.675211128	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.