TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7356	22291;22292;22293	chr2:178722833;178722832;178722831	chr2:179587560;179587559;179587558
N2AB	7039	21340;21341;21342	chr2:178722833;178722832;178722831	chr2:179587560;179587559;179587558
N2A	6112	18559;18560;18561	chr2:178722833;178722832;178722831	chr2:179587560;179587559;179587558
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: W
• RefSeq wild type transcript codon: TGG
• RefSeq wild type template codon: ACC
• Domain: Ig-58
• Domain position: 34
• Structural Position: 48
• Q(SASA): 0.1405
• 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
W/C	rs908134644	None	1.0	D	0.828	0.763	0.921398576477	gnomAD-3.1.2	1.32E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	2.94E-05	0	0
W/C	rs908134644	None	1.0	D	0.828	0.763	0.921398576477	gnomAD-4.0.0	6.41037E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.19724E-05	0	0
W/L	None	None	0.999	D	0.811	0.771	0.960035691554	gnomAD-4.0.0	1.59246E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86007E-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
W/A	0.9919	likely_pathogenic	0.9976	pathogenic	-3.018	Highly Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
W/C	0.9932	likely_pathogenic	0.9982	pathogenic	-1.683	Destabilizing	1.0	D	0.828	deleterious	D	0.708637404	None	None	N
W/D	0.9995	likely_pathogenic	0.9998	pathogenic	-2.953	Highly Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
W/E	0.9992	likely_pathogenic	0.9998	pathogenic	-2.832	Highly Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
W/F	0.5966	likely_pathogenic	0.6765	pathogenic	-1.746	Destabilizing	0.796	D	0.549	neutral	None	None	None	None	N
W/G	0.9774	likely_pathogenic	0.9922	pathogenic	-3.264	Highly Destabilizing	1.0	D	0.823	deleterious	D	0.708435599	None	None	N
W/H	0.9956	likely_pathogenic	0.9981	pathogenic	-2.066	Highly Destabilizing	1.0	D	0.848	deleterious	None	None	None	None	N
W/I	0.963	likely_pathogenic	0.9862	pathogenic	-2.088	Highly Destabilizing	1.0	D	0.868	deleterious	None	None	None	None	N
W/K	0.9996	likely_pathogenic	0.9999	pathogenic	-2.196	Highly Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
W/L	0.9182	likely_pathogenic	0.9663	pathogenic	-2.088	Highly Destabilizing	0.999	D	0.811	deleterious	D	0.692416238	None	None	N
W/M	0.985	likely_pathogenic	0.9946	pathogenic	-1.631	Destabilizing	1.0	D	0.786	deleterious	None	None	None	None	N
W/N	0.999	likely_pathogenic	0.9996	pathogenic	-2.837	Highly Destabilizing	1.0	D	0.88	deleterious	None	None	None	None	N
W/P	0.9986	likely_pathogenic	0.9994	pathogenic	-2.426	Highly Destabilizing	1.0	D	0.878	deleterious	None	None	None	None	N
W/Q	0.9992	likely_pathogenic	0.9998	pathogenic	-2.686	Highly Destabilizing	1.0	D	0.866	deleterious	None	None	None	None	N
W/R	0.9983	likely_pathogenic	0.9995	pathogenic	-1.909	Destabilizing	1.0	D	0.878	deleterious	D	0.708637404	None	None	N
W/S	0.989	likely_pathogenic	0.9968	pathogenic	-3.088	Highly Destabilizing	1.0	D	0.868	deleterious	D	0.708637404	None	None	N
W/T	0.9922	likely_pathogenic	0.9978	pathogenic	-2.899	Highly Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
W/V	0.9647	likely_pathogenic	0.9874	pathogenic	-2.426	Highly Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	N
W/Y	0.9144	likely_pathogenic	0.9511	pathogenic	-1.554	Destabilizing	0.996	D	0.763	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.