TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27766	83521;83522;83523	chr2:178562836;178562835;178562834	chr2:179427563;179427562;179427561
N2AB	26125	78598;78599;78600	chr2:178562836;178562835;178562834	chr2:179427563;179427562;179427561
N2A	25198	75817;75818;75819	chr2:178562836;178562835;178562834	chr2:179427563;179427562;179427561
N2B	18701	56326;56327;56328	chr2:178562836;178562835;178562834	chr2:179427563;179427562;179427561
Novex-1	18826	56701;56702;56703	chr2:178562836;178562835;178562834	chr2:179427563;179427562;179427561
Novex-2	18893	56902;56903;56904	chr2:178562836;178562835;178562834	chr2:179427563;179427562;179427561
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCA
• RefSeq wild type template codon: AGT
• Domain: Fn3-90
• Domain position: 1
• Structural Position: 1
• Q(SASA): 0.4012
• 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
S/L	None	None	0.518	N	0.593	0.372	0.382925413656	gnomAD-4.0.0	1.36915E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.79942E-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
S/A	0.1917	likely_benign	0.1733	benign	-0.852	Destabilizing	0.307	N	0.441	neutral	N	0.440756232	None	None	I
S/C	0.2582	likely_benign	0.2319	benign	-0.544	Destabilizing	0.996	D	0.589	neutral	None	None	None	None	I
S/D	0.9484	likely_pathogenic	0.9504	pathogenic	0.015	Stabilizing	0.74	D	0.498	neutral	None	None	None	None	I
S/E	0.9499	likely_pathogenic	0.9526	pathogenic	-0.055	Destabilizing	0.74	D	0.495	neutral	None	None	None	None	I
S/F	0.7431	likely_pathogenic	0.7276	pathogenic	-1.371	Destabilizing	0.953	D	0.759	deleterious	None	None	None	None	I
S/G	0.2895	likely_benign	0.2605	benign	-0.977	Destabilizing	0.74	D	0.369	neutral	None	None	None	None	I
S/H	0.8395	likely_pathogenic	0.8369	pathogenic	-1.488	Destabilizing	0.987	D	0.537	neutral	None	None	None	None	I
S/I	0.5558	ambiguous	0.532	ambiguous	-0.635	Destabilizing	0.909	D	0.745	deleterious	None	None	None	None	I
S/K	0.9706	likely_pathogenic	0.9689	pathogenic	-0.525	Destabilizing	0.587	D	0.401	neutral	None	None	None	None	I
S/L	0.3235	likely_benign	0.298	benign	-0.635	Destabilizing	0.518	D	0.593	neutral	N	0.446951485	None	None	I
S/M	0.4312	ambiguous	0.405	ambiguous	-0.183	Destabilizing	0.996	D	0.54	neutral	None	None	None	None	I
S/N	0.5877	likely_pathogenic	0.5697	pathogenic	-0.287	Destabilizing	0.74	D	0.545	neutral	None	None	None	None	I
S/P	0.6746	likely_pathogenic	0.6412	pathogenic	-0.681	Destabilizing	0.938	D	0.543	neutral	N	0.430421808	None	None	I
S/Q	0.9024	likely_pathogenic	0.8993	pathogenic	-0.63	Destabilizing	0.909	D	0.458	neutral	None	None	None	None	I
S/R	0.9608	likely_pathogenic	0.9568	pathogenic	-0.319	Destabilizing	0.02	N	0.311	neutral	None	None	None	None	I
S/T	0.0819	likely_benign	0.0717	benign	-0.471	Destabilizing	0.028	N	0.198	neutral	N	0.368434774	None	None	I
S/V	0.4608	ambiguous	0.4273	ambiguous	-0.681	Destabilizing	0.833	D	0.571	neutral	None	None	None	None	I
S/W	0.8911	likely_pathogenic	0.8788	pathogenic	-1.244	Destabilizing	0.996	D	0.752	deleterious	None	None	None	None	I
S/Y	0.6545	likely_pathogenic	0.6391	pathogenic	-1.011	Destabilizing	0.984	D	0.741	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.