TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27755	83488;83489;83490	chr2:178562869;178562868;178562867	chr2:179427596;179427595;179427594
N2AB	26114	78565;78566;78567	chr2:178562869;178562868;178562867	chr2:179427596;179427595;179427594
N2A	25187	75784;75785;75786	chr2:178562869;178562868;178562867	chr2:179427596;179427595;179427594
N2B	18690	56293;56294;56295	chr2:178562869;178562868;178562867	chr2:179427596;179427595;179427594
Novex-1	18815	56668;56669;56670	chr2:178562869;178562868;178562867	chr2:179427596;179427595;179427594
Novex-2	18882	56869;56870;56871	chr2:178562869;178562868;178562867	chr2:179427596;179427595;179427594
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-141
• Domain position: 80
• Structural Position: 166
• Q(SASA): 0.5843
• 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	None	None	0.99	N	0.677	0.365	0.307332253619	gnomAD-4.0.0	1.59287E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.8601E-06	0	0
K/Q	None	None	0.99	N	0.689	0.401	0.370051654043	gnomAD-4.0.0	1.59297E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86022E-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
K/A	0.7869	likely_pathogenic	0.8338	pathogenic	0.022	Stabilizing	0.86	D	0.615	neutral	None	None	None	None	N
K/C	0.9066	likely_pathogenic	0.9247	pathogenic	-0.261	Destabilizing	0.998	D	0.742	deleterious	None	None	None	None	N
K/D	0.973	likely_pathogenic	0.9787	pathogenic	0.105	Stabilizing	0.993	D	0.715	prob.delet.	None	None	None	None	N
K/E	0.7767	likely_pathogenic	0.8066	pathogenic	0.099	Stabilizing	0.966	D	0.62	neutral	D	0.531517962	None	None	N
K/F	0.9825	likely_pathogenic	0.9863	pathogenic	-0.288	Destabilizing	0.956	D	0.742	deleterious	None	None	None	None	N
K/G	0.9191	likely_pathogenic	0.9376	pathogenic	-0.143	Destabilizing	0.978	D	0.669	neutral	None	None	None	None	N
K/H	0.7372	likely_pathogenic	0.7653	pathogenic	-0.413	Destabilizing	0.998	D	0.662	neutral	None	None	None	None	N
K/I	0.8393	likely_pathogenic	0.8682	pathogenic	0.37	Stabilizing	0.032	N	0.542	neutral	D	0.534328981	None	None	N
K/L	0.8559	likely_pathogenic	0.8794	pathogenic	0.37	Stabilizing	0.514	D	0.59	neutral	None	None	None	None	N
K/M	0.7034	likely_pathogenic	0.7546	pathogenic	0.192	Stabilizing	0.988	D	0.661	neutral	None	None	None	None	N
K/N	0.9352	likely_pathogenic	0.9441	pathogenic	0.219	Stabilizing	0.99	D	0.677	prob.neutral	N	0.507608927	None	None	N
K/P	0.9946	likely_pathogenic	0.9963	pathogenic	0.281	Stabilizing	0.993	D	0.711	prob.delet.	None	None	None	None	N
K/Q	0.4203	ambiguous	0.4636	ambiguous	0.04	Stabilizing	0.99	D	0.689	prob.neutral	N	0.485363615	None	None	N
K/R	0.1341	likely_benign	0.1396	benign	0.008	Stabilizing	0.966	D	0.597	neutral	N	0.499619983	None	None	N
K/S	0.8887	likely_pathogenic	0.9109	pathogenic	-0.26	Destabilizing	0.926	D	0.647	neutral	None	None	None	None	N
K/T	0.6661	likely_pathogenic	0.7077	pathogenic	-0.126	Destabilizing	0.942	D	0.684	prob.neutral	N	0.497644973	None	None	N
K/V	0.7216	likely_pathogenic	0.7717	pathogenic	0.281	Stabilizing	0.514	D	0.601	neutral	None	None	None	None	N
K/W	0.9839	likely_pathogenic	0.987	pathogenic	-0.322	Destabilizing	0.998	D	0.732	prob.delet.	None	None	None	None	N
K/Y	0.9595	likely_pathogenic	0.9686	pathogenic	0.051	Stabilizing	0.978	D	0.724	prob.delet.	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.