TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22474	67645;67646;67647	chr2:178579777;178579776;178579775	chr2:179444504;179444503;179444502
N2AB	20833	62722;62723;62724	chr2:178579777;178579776;178579775	chr2:179444504;179444503;179444502
N2A	19906	59941;59942;59943	chr2:178579777;178579776;178579775	chr2:179444504;179444503;179444502
N2B	13409	40450;40451;40452	chr2:178579777;178579776;178579775	chr2:179444504;179444503;179444502
Novex-1	13534	40825;40826;40827	chr2:178579777;178579776;178579775	chr2:179444504;179444503;179444502
Novex-2	13601	41026;41027;41028	chr2:178579777;178579776;178579775	chr2:179444504;179444503;179444502
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Fn3-51
• Domain position: 24
• Structural Position: 26
• Q(SASA): 0.4307
• 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
K/N	rs780089189	-1.63	1.0	N	0.723	0.342	0.221734844693	gnomAD-2.1.1	8.07E-06	None	None	None	None	N	None	0	5.8E-05	None	0	0	None	0	None	0	0	0
K/N	rs780089189	-1.63	1.0	N	0.723	0.342	0.221734844693	gnomAD-4.0.0	1.36882E-06	None	None	None	None	N	None	0	4.47387E-05	None	0	0	None	0	0	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
K/A	0.789	likely_pathogenic	0.791	pathogenic	-0.79	Destabilizing	0.999	D	0.736	prob.delet.	None	None	None	None	N
K/C	0.9472	likely_pathogenic	0.9393	pathogenic	-1.135	Destabilizing	1.0	D	0.818	deleterious	None	None	None	None	N
K/D	0.9503	likely_pathogenic	0.9539	pathogenic	-0.865	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
K/E	0.73	likely_pathogenic	0.7335	pathogenic	-0.744	Destabilizing	0.999	D	0.615	neutral	N	0.482270072	None	None	N
K/F	0.9571	likely_pathogenic	0.9624	pathogenic	-0.749	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
K/G	0.9015	likely_pathogenic	0.9011	pathogenic	-1.047	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
K/H	0.739	likely_pathogenic	0.7163	pathogenic	-0.889	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
K/I	0.7443	likely_pathogenic	0.7574	pathogenic	-0.132	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
K/L	0.7166	likely_pathogenic	0.7063	pathogenic	-0.132	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
K/M	0.5795	likely_pathogenic	0.5793	pathogenic	-0.676	Destabilizing	1.0	D	0.758	deleterious	N	0.470002886	None	None	N
K/N	0.8845	likely_pathogenic	0.8912	pathogenic	-0.939	Destabilizing	1.0	D	0.723	prob.delet.	N	0.480763307	None	None	N
K/P	0.6856	likely_pathogenic	0.67	pathogenic	-0.329	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
K/Q	0.444	ambiguous	0.4233	ambiguous	-0.881	Destabilizing	1.0	D	0.698	prob.neutral	N	0.498933036	None	None	N
K/R	0.1419	likely_benign	0.1357	benign	-0.379	Destabilizing	0.999	D	0.584	neutral	N	0.478480406	None	None	N
K/S	0.8916	likely_pathogenic	0.8926	pathogenic	-1.367	Destabilizing	0.999	D	0.677	prob.neutral	None	None	None	None	N
K/T	0.7064	likely_pathogenic	0.7	pathogenic	-1.066	Destabilizing	1.0	D	0.789	deleterious	N	0.515825286	None	None	N
K/V	0.728	likely_pathogenic	0.7351	pathogenic	-0.329	Destabilizing	1.0	D	0.806	deleterious	None	None	None	None	N
K/W	0.961	likely_pathogenic	0.9608	pathogenic	-0.785	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
K/Y	0.8841	likely_pathogenic	0.8853	pathogenic	-0.496	Destabilizing	1.0	D	0.808	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.