TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1637	5134;5135;5136	chr2:178776955;178776954;178776953	chr2:179641682;179641681;179641680
N2AB	1637	5134;5135;5136	chr2:178776955;178776954;178776953	chr2:179641682;179641681;179641680
N2A	1637	5134;5135;5136	chr2:178776955;178776954;178776953	chr2:179641682;179641681;179641680
N2B	1591	4996;4997;4998	chr2:178776955;178776954;178776953	chr2:179641682;179641681;179641680
Novex-1	1591	4996;4997;4998	chr2:178776955;178776954;178776953	chr2:179641682;179641681;179641680
Novex-2	1591	4996;4997;4998	chr2:178776955;178776954;178776953	chr2:179641682;179641681;179641680
Novex-3	1637	5134;5135;5136	chr2:178776955;178776954;178776953	chr2:179641682;179641681;179641680

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGC
• RefSeq wild type template codon: CCG
• Domain: Ig-7
• Domain position: 82
• Structural Position: 164
• Q(SASA): 0.221
• Predicted PPI site: I

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
G/D	None	None	1.0	D	0.856	0.894	0.591791014774	gnomAD-4.0.0	1.36836E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	2.31976E-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
G/A	0.9251	likely_pathogenic	0.8865	pathogenic	-0.423	Destabilizing	1.0	D	0.739	prob.delet.	D	0.678558011	None	None	I
G/C	0.9809	likely_pathogenic	0.9691	pathogenic	-0.948	Destabilizing	1.0	D	0.812	deleterious	D	0.768400244	None	None	I
G/D	0.9915	likely_pathogenic	0.9876	pathogenic	-1.031	Destabilizing	1.0	D	0.856	deleterious	D	0.75489671	None	None	I
G/E	0.9928	likely_pathogenic	0.9899	pathogenic	-1.194	Destabilizing	1.0	D	0.84	deleterious	None	None	None	None	I
G/F	0.9958	likely_pathogenic	0.9942	pathogenic	-1.13	Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	I
G/H	0.9966	likely_pathogenic	0.9942	pathogenic	-0.673	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	I
G/I	0.9974	likely_pathogenic	0.9957	pathogenic	-0.553	Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	I
G/K	0.9971	likely_pathogenic	0.9954	pathogenic	-1.116	Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	I
G/L	0.9951	likely_pathogenic	0.9914	pathogenic	-0.553	Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	I
G/M	0.9968	likely_pathogenic	0.9944	pathogenic	-0.562	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	I
G/N	0.9908	likely_pathogenic	0.9851	pathogenic	-0.734	Destabilizing	1.0	D	0.802	deleterious	None	None	None	None	I
G/P	0.9997	likely_pathogenic	0.9995	pathogenic	-0.477	Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	I
G/Q	0.9912	likely_pathogenic	0.9871	pathogenic	-1.053	Destabilizing	1.0	D	0.866	deleterious	None	None	None	None	I
G/R	0.9905	likely_pathogenic	0.9852	pathogenic	-0.571	Destabilizing	1.0	D	0.871	deleterious	D	0.806348774	None	None	I
G/S	0.8779	likely_pathogenic	0.8242	pathogenic	-0.815	Destabilizing	1.0	D	0.794	deleterious	D	0.70612542	None	None	I
G/T	0.9876	likely_pathogenic	0.9814	pathogenic	-0.921	Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	I
G/V	0.9933	likely_pathogenic	0.9898	pathogenic	-0.477	Destabilizing	1.0	D	0.843	deleterious	D	0.805342699	None	None	I
G/W	0.9934	likely_pathogenic	0.9905	pathogenic	-1.285	Destabilizing	1.0	D	0.818	deleterious	None	None	None	None	I
G/Y	0.995	likely_pathogenic	0.9916	pathogenic	-0.963	Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	I

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.