TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4816	14671;14672;14673	chr2:178736000;178735999;178735998	chr2:179600727;179600726;179600725
N2AB	4499	13720;13721;13722	chr2:178736000;178735999;178735998	chr2:179600727;179600726;179600725
N2A	3572	10939;10940;10941	chr2:178736000;178735999;178735998	chr2:179600727;179600726;179600725
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-31
• Domain position: 22
• Structural Position: 33
• Q(SASA): 0.1043
• 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/W	rs2154314532	None	0.999	D	0.847	0.423	0.741552916196	gnomAD-3.1.2	6.57E-06	None	None	disulfide	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
C/W	rs2154314532	None	0.999	D	0.847	0.423	0.741552916196	gnomAD-4.0.0	4.05918E-06	None	None	disulfide	None	N	None	0	0	None	0	0	None	0	0	4.81972E-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	0.626	likely_pathogenic	0.5166	ambiguous	-1.802	Destabilizing	0.015	N	0.376	neutral	None	None	disulfide	None	N
C/D	0.9952	likely_pathogenic	0.9961	pathogenic	-1.759	Destabilizing	0.988	D	0.867	deleterious	None	None	disulfide	None	N
C/E	0.9977	likely_pathogenic	0.9982	pathogenic	-1.519	Destabilizing	0.976	D	0.863	deleterious	None	None	disulfide	None	N
C/F	0.7907	likely_pathogenic	0.8437	pathogenic	-1.1	Destabilizing	0.995	D	0.834	deleterious	D	0.577572272	disulfide	None	N
C/G	0.3742	ambiguous	0.2523	benign	-2.164	Highly Destabilizing	0.811	D	0.834	deleterious	N	0.491644099	disulfide	None	N
C/H	0.9867	likely_pathogenic	0.9908	pathogenic	-2.366	Highly Destabilizing	0.999	D	0.874	deleterious	None	None	disulfide	None	N
C/I	0.8239	likely_pathogenic	0.8405	pathogenic	-0.812	Destabilizing	0.976	D	0.833	deleterious	None	None	disulfide	None	N
C/K	0.9987	likely_pathogenic	0.9991	pathogenic	-1.402	Destabilizing	0.976	D	0.858	deleterious	None	None	disulfide	None	N
C/L	0.809	likely_pathogenic	0.8033	pathogenic	-0.812	Destabilizing	0.919	D	0.759	deleterious	None	None	disulfide	None	N
C/M	0.9296	likely_pathogenic	0.9307	pathogenic	0.206	Stabilizing	0.999	D	0.793	deleterious	None	None	disulfide	None	N
C/N	0.9756	likely_pathogenic	0.9774	pathogenic	-2.025	Highly Destabilizing	0.988	D	0.873	deleterious	None	None	disulfide	None	N
C/P	0.9944	likely_pathogenic	0.9947	pathogenic	-1.121	Destabilizing	0.988	D	0.868	deleterious	None	None	disulfide	None	N
C/Q	0.9917	likely_pathogenic	0.9933	pathogenic	-1.523	Destabilizing	0.988	D	0.856	deleterious	None	None	disulfide	None	N
C/R	0.9855	likely_pathogenic	0.9906	pathogenic	-1.806	Destabilizing	0.984	D	0.872	deleterious	D	0.618790102	disulfide	None	N
C/S	0.6138	likely_pathogenic	0.5757	pathogenic	-2.324	Highly Destabilizing	0.811	D	0.767	deleterious	D	0.552923351	disulfide	None	N
C/T	0.7679	likely_pathogenic	0.7237	pathogenic	-1.906	Destabilizing	0.919	D	0.791	deleterious	None	None	disulfide	None	N
C/V	0.6855	likely_pathogenic	0.6764	pathogenic	-1.121	Destabilizing	0.851	D	0.771	deleterious	None	None	disulfide	None	N
C/W	0.9782	likely_pathogenic	0.9904	pathogenic	-1.534	Destabilizing	0.999	D	0.847	deleterious	D	0.618790102	disulfide	None	N
C/Y	0.9364	likely_pathogenic	0.9602	pathogenic	-1.363	Destabilizing	0.995	D	0.823	deleterious	D	0.617696879	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.