TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32435	97528;97529;97530	chr2:178542453;178542452;178542451	chr2:179407180;179407179;179407178
N2AB	30794	92605;92606;92607	chr2:178542453;178542452;178542451	chr2:179407180;179407179;179407178
N2A	29867	89824;89825;89826	chr2:178542453;178542452;178542451	chr2:179407180;179407179;179407178
N2B	23370	70333;70334;70335	chr2:178542453;178542452;178542451	chr2:179407180;179407179;179407178
Novex-1	23495	70708;70709;70710	chr2:178542453;178542452;178542451	chr2:179407180;179407179;179407178
Novex-2	23562	70909;70910;70911	chr2:178542453;178542452;178542451	chr2:179407180;179407179;179407178
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Fn3-124
• Domain position: 37
• Structural Position: 38
• Q(SASA): 0.1363
• 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
Y/C	rs1248603103	-1.911	1.0	D	0.869	0.785	0.740413529801	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	6.46E-05	0	None	0	0	None	0	None	0	0	0
Y/C	rs1248603103	-1.911	1.0	D	0.869	0.785	0.740413529801	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	6.55E-05	0	0	0	None	0	0	0	0	0
Y/C	rs1248603103	-1.911	1.0	D	0.869	0.785	0.740413529801	gnomAD-4.0.0	2.56253E-06	None	None	None	None	N	None	1.69113E-05	1.69474E-05	None	0	0	None	0	0	0	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
Y/A	0.9945	likely_pathogenic	0.9921	pathogenic	-3.361	Highly Destabilizing	1.0	D	0.77	deleterious	None	None	None	None	N
Y/C	0.9064	likely_pathogenic	0.8474	pathogenic	-1.976	Destabilizing	1.0	D	0.869	deleterious	D	0.659947237	None	None	N
Y/D	0.9945	likely_pathogenic	0.9938	pathogenic	-3.658	Highly Destabilizing	1.0	D	0.874	deleterious	D	0.660149042	None	None	N
Y/E	0.9987	likely_pathogenic	0.9984	pathogenic	-3.434	Highly Destabilizing	1.0	D	0.862	deleterious	None	None	None	None	N
Y/F	0.1735	likely_benign	0.1541	benign	-1.241	Destabilizing	0.999	D	0.68	prob.neutral	N	0.512241552	None	None	N
Y/G	0.9891	likely_pathogenic	0.9859	pathogenic	-3.785	Highly Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	N
Y/H	0.9704	likely_pathogenic	0.9587	pathogenic	-2.504	Highly Destabilizing	1.0	D	0.824	deleterious	D	0.643493908	None	None	N
Y/I	0.9603	likely_pathogenic	0.9502	pathogenic	-1.93	Destabilizing	1.0	D	0.828	deleterious	None	None	None	None	N
Y/K	0.9983	likely_pathogenic	0.998	pathogenic	-2.228	Highly Destabilizing	1.0	D	0.858	deleterious	None	None	None	None	N
Y/L	0.9337	likely_pathogenic	0.9199	pathogenic	-1.93	Destabilizing	0.999	D	0.721	prob.delet.	None	None	None	None	N
Y/M	0.9715	likely_pathogenic	0.9628	pathogenic	-1.791	Destabilizing	1.0	D	0.826	deleterious	None	None	None	None	N
Y/N	0.969	likely_pathogenic	0.9579	pathogenic	-3.024	Highly Destabilizing	1.0	D	0.853	deleterious	D	0.660149042	None	None	N
Y/P	0.9989	likely_pathogenic	0.999	pathogenic	-2.426	Highly Destabilizing	1.0	D	0.904	deleterious	None	None	None	None	N
Y/Q	0.9977	likely_pathogenic	0.9968	pathogenic	-2.752	Highly Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
Y/R	0.9947	likely_pathogenic	0.9937	pathogenic	-2.053	Highly Destabilizing	1.0	D	0.856	deleterious	None	None	None	None	N
Y/S	0.9824	likely_pathogenic	0.9757	pathogenic	-3.375	Highly Destabilizing	1.0	D	0.863	deleterious	D	0.660149042	None	None	N
Y/T	0.9927	likely_pathogenic	0.99	pathogenic	-3.023	Highly Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
Y/V	0.942	likely_pathogenic	0.9268	pathogenic	-2.426	Highly Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	N
Y/W	0.7826	likely_pathogenic	0.7794	pathogenic	-0.437	Destabilizing	1.0	D	0.811	deleterious	None	None	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.