TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2928	9007;9008;9009	chr2:178769799;178769798;178769797	chr2:179634526;179634525;179634524
N2AB	2928	9007;9008;9009	chr2:178769799;178769798;178769797	chr2:179634526;179634525;179634524
N2A	2928	9007;9008;9009	chr2:178769799;178769798;178769797	chr2:179634526;179634525;179634524
N2B	2882	8869;8870;8871	chr2:178769799;178769798;178769797	chr2:179634526;179634525;179634524
Novex-1	2882	8869;8870;8871	chr2:178769799;178769798;178769797	chr2:179634526;179634525;179634524
Novex-2	2882	8869;8870;8871	chr2:178769799;178769798;178769797	chr2:179634526;179634525;179634524
Novex-3	2928	9007;9008;9009	chr2:178769799;178769798;178769797	chr2:179634526;179634525;179634524

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Ig-19
• Domain position: 47
• Structural Position: 122
• Q(SASA): 0.335
• 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/Q	None	None	0.961	N	0.508	0.382	0.238705975628	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-06	0	0
K/R	None	None	0.031	N	0.168	0.326	0.240491677333	gnomAD-4.0.0	1.59046E-06	None	None	None	None	N	None	0	0	None	0	2.77239E-05	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	0.8518	likely_pathogenic	0.7931	pathogenic	-0.7	Destabilizing	0.97	D	0.541	neutral	None	None	None	None	N
K/C	0.9104	likely_pathogenic	0.9017	pathogenic	-0.682	Destabilizing	1.0	D	0.666	neutral	None	None	None	None	N
K/D	0.9462	likely_pathogenic	0.9141	pathogenic	-0.393	Destabilizing	0.996	D	0.51	neutral	None	None	None	None	N
K/E	0.6376	likely_pathogenic	0.5174	ambiguous	-0.227	Destabilizing	0.961	D	0.535	neutral	N	0.474710235	None	None	N
K/F	0.9797	likely_pathogenic	0.9719	pathogenic	-0.116	Destabilizing	0.999	D	0.637	neutral	None	None	None	None	N
K/G	0.8782	likely_pathogenic	0.8462	pathogenic	-1.135	Destabilizing	0.985	D	0.509	neutral	None	None	None	None	N
K/H	0.5885	likely_pathogenic	0.5426	ambiguous	-1.46	Destabilizing	0.999	D	0.579	neutral	None	None	None	None	N
K/I	0.8271	likely_pathogenic	0.7716	pathogenic	0.46	Stabilizing	0.999	D	0.631	neutral	None	None	None	None	N
K/L	0.8198	likely_pathogenic	0.7582	pathogenic	0.46	Stabilizing	0.97	D	0.509	neutral	None	None	None	None	N
K/M	0.6641	likely_pathogenic	0.5922	pathogenic	0.279	Stabilizing	1.0	D	0.579	neutral	N	0.510614972	None	None	N
K/N	0.8571	likely_pathogenic	0.7818	pathogenic	-0.806	Destabilizing	0.98	D	0.475	neutral	N	0.495529398	None	None	N
K/P	0.9917	likely_pathogenic	0.9871	pathogenic	0.103	Stabilizing	0.999	D	0.565	neutral	None	None	None	None	N
K/Q	0.2993	likely_benign	0.2463	benign	-0.733	Destabilizing	0.961	D	0.508	neutral	N	0.454907424	None	None	N
K/R	0.1166	likely_benign	0.1061	benign	-0.904	Destabilizing	0.031	N	0.168	neutral	N	0.440303015	None	None	N
K/S	0.8476	likely_pathogenic	0.7702	pathogenic	-1.434	Destabilizing	0.985	D	0.463	neutral	None	None	None	None	N
K/T	0.5797	likely_pathogenic	0.473	ambiguous	-1.038	Destabilizing	0.98	D	0.507	neutral	N	0.498552984	None	None	N
K/V	0.7925	likely_pathogenic	0.7372	pathogenic	0.103	Stabilizing	0.996	D	0.533	neutral	None	None	None	None	N
K/W	0.9586	likely_pathogenic	0.9561	pathogenic	-0.036	Destabilizing	1.0	D	0.684	prob.neutral	None	None	None	None	N
K/Y	0.928	likely_pathogenic	0.9183	pathogenic	0.243	Stabilizing	0.999	D	0.623	neutral	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.