TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26691	80296;80297;80298	chr2:178566061;178566060;178566059	chr2:179430788;179430787;179430786
N2AB	25050	75373;75374;75375	chr2:178566061;178566060;178566059	chr2:179430788;179430787;179430786
N2A	24123	72592;72593;72594	chr2:178566061;178566060;178566059	chr2:179430788;179430787;179430786
N2B	17626	53101;53102;53103	chr2:178566061;178566060;178566059	chr2:179430788;179430787;179430786
Novex-1	17751	53476;53477;53478	chr2:178566061;178566060;178566059	chr2:179430788;179430787;179430786
Novex-2	17818	53677;53678;53679	chr2:178566061;178566060;178566059	chr2:179430788;179430787;179430786
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Fn3-82
• Domain position: 9
• Structural Position: 11
• Q(SASA): 0.3281
• 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
A/T	None	None	None	N	0.099	0.096	0.0297737177859	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
A/C	0.2013	likely_benign	0.2355	benign	-0.779	Destabilizing	0.356	N	0.479	neutral	None	None	None	None	N
A/D	0.2007	likely_benign	0.1977	benign	-0.683	Destabilizing	0.038	N	0.502	neutral	None	None	None	None	N
A/E	0.1436	likely_benign	0.1343	benign	-0.726	Destabilizing	None	N	0.295	neutral	N	0.410369902	None	None	N
A/F	0.1654	likely_benign	0.1772	benign	-0.692	Destabilizing	None	N	0.397	neutral	None	None	None	None	N
A/G	0.1223	likely_benign	0.1352	benign	-0.767	Destabilizing	0.024	N	0.297	neutral	N	0.462588234	None	None	N
A/H	0.2172	likely_benign	0.232	benign	-0.855	Destabilizing	0.356	N	0.538	neutral	None	None	None	None	N
A/I	0.0885	likely_benign	0.0917	benign	-0.119	Destabilizing	None	N	0.245	neutral	None	None	None	None	N
A/K	0.2292	likely_benign	0.2336	benign	-1.013	Destabilizing	0.038	N	0.423	neutral	None	None	None	None	N
A/L	0.0745	likely_benign	0.0793	benign	-0.119	Destabilizing	None	N	0.218	neutral	None	None	None	None	N
A/M	0.0917	likely_benign	0.098	benign	-0.262	Destabilizing	0.214	N	0.502	neutral	None	None	None	None	N
A/N	0.1253	likely_benign	0.1403	benign	-0.787	Destabilizing	0.072	N	0.571	neutral	None	None	None	None	N
A/P	0.6566	likely_pathogenic	0.7163	pathogenic	-0.22	Destabilizing	0.106	N	0.541	neutral	D	0.522367256	None	None	N
A/Q	0.1586	likely_benign	0.1636	benign	-0.908	Destabilizing	0.12	N	0.576	neutral	None	None	None	None	N
A/R	0.2243	likely_benign	0.2239	benign	-0.677	Destabilizing	0.072	N	0.552	neutral	None	None	None	None	N
A/S	0.0764	likely_benign	0.0809	benign	-1.097	Destabilizing	0.012	N	0.295	neutral	N	0.437919076	None	None	N
A/T	0.0578	likely_benign	0.0585	benign	-1.037	Destabilizing	None	N	0.099	neutral	N	0.348299936	None	None	N
A/V	0.064	likely_benign	0.0647	benign	-0.22	Destabilizing	None	N	0.12	neutral	N	0.402809211	None	None	N
A/W	0.4689	ambiguous	0.4871	ambiguous	-1.023	Destabilizing	0.864	D	0.546	neutral	None	None	None	None	N
A/Y	0.2365	likely_benign	0.2517	benign	-0.603	Destabilizing	0.038	N	0.607	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.