TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6163	18712;18713;18714	chr2:178729766;178729765;178729764	chr2:179594493;179594492;179594491
N2AB	5846	17761;17762;17763	chr2:178729766;178729765;178729764	chr2:179594493;179594492;179594491
N2A	4919	14980;14981;14982	chr2:178729766;178729765;178729764	chr2:179594493;179594492;179594491
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: F
• RefSeq wild type transcript codon: TTC
• RefSeq wild type template codon: AAG
• Domain: Ig-45
• Domain position: 59
• Structural Position: 138
• Q(SASA): 0.075
• 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
F/S	rs1458021092	None	0.891	D	0.813	0.622	0.827827249136	gnomAD-4.0.0	1.59137E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	2.41663E-04	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
F/A	0.8179	likely_pathogenic	0.8335	pathogenic	-1.403	Destabilizing	0.842	D	0.771	deleterious	None	None	None	None	N
F/C	0.3594	ambiguous	0.3808	ambiguous	-1.086	Destabilizing	0.997	D	0.841	deleterious	N	0.510878905	None	None	N
F/D	0.9923	likely_pathogenic	0.9937	pathogenic	-2.701	Highly Destabilizing	0.991	D	0.855	deleterious	None	None	None	None	N
F/E	0.9877	likely_pathogenic	0.9899	pathogenic	-2.48	Highly Destabilizing	0.991	D	0.845	deleterious	None	None	None	None	N
F/G	0.9324	likely_pathogenic	0.9404	pathogenic	-1.804	Destabilizing	0.991	D	0.835	deleterious	None	None	None	None	N
F/H	0.9157	likely_pathogenic	0.9197	pathogenic	-1.767	Destabilizing	0.998	D	0.778	deleterious	None	None	None	None	N
F/I	0.2248	likely_benign	0.2736	benign	-0.097	Destabilizing	0.454	N	0.675	neutral	N	0.398804193	None	None	N
F/K	0.9833	likely_pathogenic	0.9849	pathogenic	-1.532	Destabilizing	0.974	D	0.829	deleterious	None	None	None	None	N
F/L	0.558	ambiguous	0.6113	pathogenic	-0.097	Destabilizing	0.002	N	0.355	neutral	N	0.252004674	None	None	N
F/M	0.4692	ambiguous	0.506	ambiguous	-0.32	Destabilizing	0.949	D	0.692	prob.neutral	None	None	None	None	N
F/N	0.9681	likely_pathogenic	0.9724	pathogenic	-2.248	Highly Destabilizing	0.991	D	0.861	deleterious	None	None	None	None	N
F/P	0.9966	likely_pathogenic	0.9972	pathogenic	-0.543	Destabilizing	0.991	D	0.863	deleterious	None	None	None	None	N
F/Q	0.9674	likely_pathogenic	0.9714	pathogenic	-1.886	Destabilizing	0.991	D	0.862	deleterious	None	None	None	None	N
F/R	0.9524	likely_pathogenic	0.9545	pathogenic	-1.897	Destabilizing	0.974	D	0.856	deleterious	None	None	None	None	N
F/S	0.8784	likely_pathogenic	0.8837	pathogenic	-2.449	Highly Destabilizing	0.891	D	0.813	deleterious	D	0.529734024	None	None	N
F/T	0.9052	likely_pathogenic	0.9168	pathogenic	-2.103	Highly Destabilizing	0.915	D	0.793	deleterious	None	None	None	None	N
F/V	0.2463	likely_benign	0.2858	benign	-0.543	Destabilizing	0.454	N	0.727	prob.delet.	N	0.444115195	None	None	N
F/W	0.7171	likely_pathogenic	0.7207	pathogenic	-0.134	Destabilizing	0.998	D	0.677	prob.neutral	None	None	None	None	N
F/Y	0.299	likely_benign	0.3097	benign	-0.385	Destabilizing	0.891	D	0.653	neutral	N	0.492119786	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.