TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	13990	42193;42194;42195	chr2:178635221;178635220;178635219	chr2:179499948;179499947;179499946
N2AB	12349	37270;37271;37272	chr2:178635221;178635220;178635219	chr2:179499948;179499947;179499946
N2A	11422	34489;34490;34491	chr2:178635221;178635220;178635219	chr2:179499948;179499947;179499946
N2B	4925	14998;14999;15000	chr2:178635221;178635220;178635219	chr2:179499948;179499947;179499946
Novex-1	5050	15373;15374;15375	chr2:178635221;178635220;178635219	chr2:179499948;179499947;179499946
Novex-2	5117	15574;15575;15576	chr2:178635221;178635220;178635219	chr2:179499948;179499947;179499946
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Ig-90
• Domain position: 26
• Structural Position: 40
• Q(SASA): 0.5652
• 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
E/D	None	None	0.997	N	0.514	0.169	0.152612264143	gnomAD-4.0.0	1.36881E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79934E-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
E/A	0.6825	likely_pathogenic	0.5694	pathogenic	-0.549	Destabilizing	0.997	D	0.708	prob.delet.	N	0.497097406	None	None	N
E/C	0.9866	likely_pathogenic	0.9794	pathogenic	-0.14	Destabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	N
E/D	0.5963	likely_pathogenic	0.5277	ambiguous	-0.576	Destabilizing	0.997	D	0.514	neutral	N	0.459664243	None	None	N
E/F	0.9846	likely_pathogenic	0.9736	pathogenic	-0.209	Destabilizing	1.0	D	0.675	prob.neutral	None	None	None	None	N
E/G	0.7835	likely_pathogenic	0.7305	pathogenic	-0.809	Destabilizing	0.999	D	0.579	neutral	N	0.410274924	None	None	N
E/H	0.9571	likely_pathogenic	0.9269	pathogenic	-0.082	Destabilizing	1.0	D	0.647	neutral	None	None	None	None	N
E/I	0.9289	likely_pathogenic	0.8583	pathogenic	0.123	Stabilizing	0.999	D	0.68	prob.neutral	None	None	None	None	N
E/K	0.8139	likely_pathogenic	0.7007	pathogenic	0.204	Stabilizing	0.997	D	0.643	neutral	N	0.439838361	None	None	N
E/L	0.9282	likely_pathogenic	0.8735	pathogenic	0.123	Stabilizing	0.999	D	0.589	neutral	None	None	None	None	N
E/M	0.9483	likely_pathogenic	0.9029	pathogenic	0.297	Stabilizing	1.0	D	0.693	prob.delet.	None	None	None	None	N
E/N	0.9243	likely_pathogenic	0.8633	pathogenic	-0.327	Destabilizing	0.999	D	0.705	prob.delet.	None	None	None	None	N
E/P	0.9866	likely_pathogenic	0.9802	pathogenic	-0.08	Destabilizing	0.999	D	0.633	neutral	None	None	None	None	N
E/Q	0.6768	likely_pathogenic	0.5365	ambiguous	-0.24	Destabilizing	0.999	D	0.65	prob.neutral	N	0.421211686	None	None	N
E/R	0.8839	likely_pathogenic	0.797	pathogenic	0.453	Stabilizing	0.999	D	0.697	prob.delet.	None	None	None	None	N
E/S	0.8294	likely_pathogenic	0.7516	pathogenic	-0.476	Destabilizing	0.998	D	0.681	prob.neutral	None	None	None	None	N
E/T	0.8691	likely_pathogenic	0.7975	pathogenic	-0.254	Destabilizing	0.999	D	0.681	prob.neutral	None	None	None	None	N
E/V	0.7981	likely_pathogenic	0.6536	pathogenic	-0.08	Destabilizing	0.999	D	0.589	neutral	N	0.44322335	None	None	N
E/W	0.9964	likely_pathogenic	0.9944	pathogenic	0.027	Stabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	N
E/Y	0.9791	likely_pathogenic	0.964	pathogenic	0.059	Stabilizing	1.0	D	0.651	prob.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.