TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26426	79501;79502;79503	chr2:178566856;178566855;178566854	chr2:179431583;179431582;179431581
N2AB	24785	74578;74579;74580	chr2:178566856;178566855;178566854	chr2:179431583;179431582;179431581
N2A	23858	71797;71798;71799	chr2:178566856;178566855;178566854	chr2:179431583;179431582;179431581
N2B	17361	52306;52307;52308	chr2:178566856;178566855;178566854	chr2:179431583;179431582;179431581
Novex-1	17486	52681;52682;52683	chr2:178566856;178566855;178566854	chr2:179431583;179431582;179431581
Novex-2	17553	52882;52883;52884	chr2:178566856;178566855;178566854	chr2:179431583;179431582;179431581
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGA
• RefSeq wild type template codon: TCT
• Domain: Fn3-80
• Domain position: 41
• Structural Position: 43
• Q(SASA): 0.2168
• 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
R/I	None	None	0.983	D	0.797	0.506	0.596373027241	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
R/A	0.9809	likely_pathogenic	0.9798	pathogenic	-2.047	Highly Destabilizing	0.845	D	0.543	neutral	None	None	None	None	N
R/C	0.6088	likely_pathogenic	0.6162	pathogenic	-1.852	Destabilizing	0.999	D	0.745	deleterious	None	None	None	None	N
R/D	0.9976	likely_pathogenic	0.9971	pathogenic	-1.046	Destabilizing	0.975	D	0.777	deleterious	None	None	None	None	N
R/E	0.9732	likely_pathogenic	0.9683	pathogenic	-0.823	Destabilizing	0.845	D	0.449	neutral	None	None	None	None	N
R/F	0.9844	likely_pathogenic	0.9764	pathogenic	-1.186	Destabilizing	0.996	D	0.787	deleterious	None	None	None	None	N
R/G	0.9669	likely_pathogenic	0.9645	pathogenic	-2.39	Highly Destabilizing	0.892	D	0.683	prob.neutral	N	0.516379614	None	None	N
R/H	0.353	ambiguous	0.3137	benign	-2.13	Highly Destabilizing	0.987	D	0.607	neutral	None	None	None	None	N
R/I	0.9638	likely_pathogenic	0.9572	pathogenic	-1.041	Destabilizing	0.983	D	0.797	deleterious	D	0.548055447	None	None	N
R/K	0.2908	likely_benign	0.2713	benign	-1.247	Destabilizing	0.025	N	0.221	neutral	N	0.498951679	None	None	N
R/L	0.9059	likely_pathogenic	0.901	pathogenic	-1.041	Destabilizing	0.916	D	0.683	prob.neutral	None	None	None	None	N
R/M	0.939	likely_pathogenic	0.9293	pathogenic	-1.536	Destabilizing	0.999	D	0.725	prob.delet.	None	None	None	None	N
R/N	0.9865	likely_pathogenic	0.983	pathogenic	-1.338	Destabilizing	0.975	D	0.578	neutral	None	None	None	None	N
R/P	0.9991	likely_pathogenic	0.9991	pathogenic	-1.367	Destabilizing	0.987	D	0.793	deleterious	None	None	None	None	N
R/Q	0.4529	ambiguous	0.4458	ambiguous	-1.181	Destabilizing	0.975	D	0.565	neutral	None	None	None	None	N
R/S	0.9913	likely_pathogenic	0.99	pathogenic	-2.216	Highly Destabilizing	0.892	D	0.656	neutral	N	0.479104239	None	None	N
R/T	0.9814	likely_pathogenic	0.9808	pathogenic	-1.781	Destabilizing	0.967	D	0.737	prob.delet.	N	0.521303911	None	None	N
R/V	0.9694	likely_pathogenic	0.9666	pathogenic	-1.367	Destabilizing	0.975	D	0.789	deleterious	None	None	None	None	N
R/W	0.7982	likely_pathogenic	0.7645	pathogenic	-0.699	Destabilizing	0.999	D	0.699	prob.neutral	None	None	None	None	N
R/Y	0.9315	likely_pathogenic	0.8992	pathogenic	-0.589	Destabilizing	0.996	D	0.793	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.