TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25232	75919;75920;75921	chr2:178570438;178570437;178570436	chr2:179435165;179435164;179435163
N2AB	23591	70996;70997;70998	chr2:178570438;178570437;178570436	chr2:179435165;179435164;179435163
N2A	22664	68215;68216;68217	chr2:178570438;178570437;178570436	chr2:179435165;179435164;179435163
N2B	16167	48724;48725;48726	chr2:178570438;178570437;178570436	chr2:179435165;179435164;179435163
Novex-1	16292	49099;49100;49101	chr2:178570438;178570437;178570436	chr2:179435165;179435164;179435163
Novex-2	16359	49300;49301;49302	chr2:178570438;178570437;178570436	chr2:179435165;179435164;179435163
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Fn3-71
• Domain position: 29
• Structural Position: 30
• Q(SASA): 0.33
• 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
D/E	None	None	1.0	N	0.441	0.348	0.34854441366	gnomAD-4.0.0	6.84436E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99599E-07	0	0
D/N	rs912960791	None	1.0	N	0.679	0.407	0.48461828368	gnomAD-4.0.0	7.20193E-06	None	None	None	None	I	None	6.33473E-05	0	None	0	0	None	0	0	6.56251E-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
D/A	0.7335	likely_pathogenic	0.7602	pathogenic	-0.169	Destabilizing	1.0	D	0.719	prob.delet.	N	0.496843327	None	None	I
D/C	0.9449	likely_pathogenic	0.9567	pathogenic	0.199	Stabilizing	1.0	D	0.655	neutral	None	None	None	None	I
D/E	0.7378	likely_pathogenic	0.7659	pathogenic	-0.645	Destabilizing	1.0	D	0.441	neutral	N	0.498956467	None	None	I
D/F	0.9619	likely_pathogenic	0.9679	pathogenic	-0.441	Destabilizing	1.0	D	0.653	neutral	None	None	None	None	I
D/G	0.6523	likely_pathogenic	0.7027	pathogenic	-0.418	Destabilizing	1.0	D	0.689	prob.neutral	N	0.520418538	None	None	I
D/H	0.8414	likely_pathogenic	0.8654	pathogenic	-0.819	Destabilizing	1.0	D	0.653	neutral	N	0.51965807	None	None	I
D/I	0.9034	likely_pathogenic	0.9066	pathogenic	0.447	Stabilizing	1.0	D	0.679	prob.neutral	None	None	None	None	I
D/K	0.9249	likely_pathogenic	0.937	pathogenic	0.119	Stabilizing	1.0	D	0.736	prob.delet.	None	None	None	None	I
D/L	0.9112	likely_pathogenic	0.916	pathogenic	0.447	Stabilizing	1.0	D	0.695	prob.neutral	None	None	None	None	I
D/M	0.9531	likely_pathogenic	0.9583	pathogenic	0.862	Stabilizing	1.0	D	0.645	neutral	None	None	None	None	I
D/N	0.1898	likely_benign	0.1918	benign	-0.121	Destabilizing	1.0	D	0.679	prob.neutral	N	0.468623761	None	None	I
D/P	0.9675	likely_pathogenic	0.9717	pathogenic	0.266	Stabilizing	1.0	D	0.738	prob.delet.	None	None	None	None	I
D/Q	0.9032	likely_pathogenic	0.9112	pathogenic	-0.063	Destabilizing	1.0	D	0.732	prob.delet.	None	None	None	None	I
D/R	0.9324	likely_pathogenic	0.9411	pathogenic	0.004	Stabilizing	1.0	D	0.711	prob.delet.	None	None	None	None	I
D/S	0.4575	ambiguous	0.5038	ambiguous	-0.25	Destabilizing	1.0	D	0.696	prob.neutral	None	None	None	None	I
D/T	0.6521	likely_pathogenic	0.6835	pathogenic	-0.054	Destabilizing	1.0	D	0.744	deleterious	None	None	None	None	I
D/V	0.7854	likely_pathogenic	0.7931	pathogenic	0.266	Stabilizing	1.0	D	0.7	prob.neutral	D	0.52589904	None	None	I
D/W	0.9914	likely_pathogenic	0.9929	pathogenic	-0.47	Destabilizing	1.0	D	0.649	neutral	None	None	None	None	I
D/Y	0.7419	likely_pathogenic	0.7688	pathogenic	-0.241	Destabilizing	1.0	D	0.635	neutral	D	0.538522793	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.