TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6161	18706;18707;18708	chr2:178729772;178729771;178729770	chr2:179594499;179594498;179594497
N2AB	5844	17755;17756;17757	chr2:178729772;178729771;178729770	chr2:179594499;179594498;179594497
N2A	4917	14974;14975;14976	chr2:178729772;178729771;178729770	chr2:179594499;179594498;179594497
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: A
• RefSeq wild type transcript codon: GCC
• RefSeq wild type template codon: CGG
• Domain: Ig-45
• Domain position: 57
• Structural Position: 136
• Q(SASA): 0.0775
• 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
A/P	None	None	1.0	N	0.824	0.444	0.589695452637	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
A/C	0.7202	likely_pathogenic	0.6609	pathogenic	-0.726	Destabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	N
A/D	0.9489	likely_pathogenic	0.9189	pathogenic	-1.967	Destabilizing	1.0	D	0.841	deleterious	N	0.493570049	None	None	N
A/E	0.9062	likely_pathogenic	0.8493	pathogenic	-1.749	Destabilizing	1.0	D	0.802	deleterious	None	None	None	None	N
A/F	0.7918	likely_pathogenic	0.7197	pathogenic	-0.38	Destabilizing	1.0	D	0.852	deleterious	None	None	None	None	N
A/G	0.3032	likely_benign	0.2896	benign	-1.146	Destabilizing	1.0	D	0.597	neutral	N	0.509529324	None	None	N
A/H	0.9384	likely_pathogenic	0.9087	pathogenic	-1.835	Destabilizing	1.0	D	0.828	deleterious	None	None	None	None	N
A/I	0.6587	likely_pathogenic	0.5358	ambiguous	0.698	Stabilizing	1.0	D	0.826	deleterious	None	None	None	None	N
A/K	0.9696	likely_pathogenic	0.9493	pathogenic	-0.626	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
A/L	0.5164	ambiguous	0.4256	ambiguous	0.698	Stabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	N
A/M	0.6483	likely_pathogenic	0.542	ambiguous	0.361	Stabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
A/N	0.9036	likely_pathogenic	0.8524	pathogenic	-0.984	Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	N
A/P	0.8973	likely_pathogenic	0.9016	pathogenic	0.293	Stabilizing	1.0	D	0.824	deleterious	N	0.510713253	None	None	N
A/Q	0.8925	likely_pathogenic	0.8458	pathogenic	-0.722	Destabilizing	1.0	D	0.826	deleterious	None	None	None	None	N
A/R	0.9311	likely_pathogenic	0.8994	pathogenic	-0.954	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
A/S	0.2366	likely_benign	0.1979	benign	-1.372	Destabilizing	1.0	D	0.603	neutral	N	0.504928793	None	None	N
A/T	0.3183	likely_benign	0.2216	benign	-1.019	Destabilizing	1.0	D	0.72	prob.delet.	N	0.484389337	None	None	N
A/V	0.3159	likely_benign	0.2319	benign	0.293	Stabilizing	1.0	D	0.634	neutral	N	0.492329055	None	None	N
A/W	0.9768	likely_pathogenic	0.9602	pathogenic	-1.262	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
A/Y	0.9018	likely_pathogenic	0.8572	pathogenic	-0.619	Destabilizing	1.0	D	0.852	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.