TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6830	20713;20714;20715	chr2:178725834;178725833;178725832	chr2:179590561;179590560;179590559
N2AB	6513	19762;19763;19764	chr2:178725834;178725833;178725832	chr2:179590561;179590560;179590559
N2A	5586	16981;16982;16983	chr2:178725834;178725833;178725832	chr2:179590561;179590560;179590559
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-52
• Domain position: 70
• Structural Position: 153
• Q(SASA): 0.3394
• 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/K	rs1458416906	-0.261	0.877	D	0.554	0.303	0.31291088546	gnomAD-2.1.1	3.19E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	6.48E-05	0
E/K	rs1458416906	-0.261	0.877	D	0.554	0.303	0.31291088546	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
E/K	rs1458416906	-0.261	0.877	D	0.554	0.303	0.31291088546	gnomAD-4.0.0	6.57272E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.4702E-05	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	0.185	likely_benign	0.1688	benign	-0.813	Destabilizing	0.794	D	0.601	neutral	N	0.489922745	None	None	N
E/C	0.895	likely_pathogenic	0.8566	pathogenic	-0.347	Destabilizing	0.998	D	0.712	prob.delet.	None	None	None	None	N
E/D	0.1103	likely_benign	0.1042	benign	-0.91	Destabilizing	0.002	N	0.224	neutral	N	0.485575028	None	None	N
E/F	0.7337	likely_pathogenic	0.6747	pathogenic	-0.322	Destabilizing	0.971	D	0.725	prob.delet.	None	None	None	None	N
E/G	0.283	likely_benign	0.2498	benign	-1.145	Destabilizing	0.928	D	0.647	neutral	N	0.517118808	None	None	N
E/H	0.5403	ambiguous	0.4898	ambiguous	-0.505	Destabilizing	0.998	D	0.608	neutral	None	None	None	None	N
E/I	0.275	likely_benign	0.2373	benign	0.078	Stabilizing	0.689	D	0.646	neutral	None	None	None	None	N
E/K	0.185	likely_benign	0.1663	benign	-0.372	Destabilizing	0.877	D	0.554	neutral	D	0.524975992	None	None	N
E/L	0.3734	ambiguous	0.3353	benign	0.078	Stabilizing	0.014	N	0.419	neutral	None	None	None	None	N
E/M	0.4381	ambiguous	0.3854	ambiguous	0.476	Stabilizing	0.735	D	0.717	prob.delet.	None	None	None	None	N
E/N	0.2363	likely_benign	0.2045	benign	-0.833	Destabilizing	0.783	D	0.593	neutral	None	None	None	None	N
E/P	0.6392	likely_pathogenic	0.5941	pathogenic	-0.198	Destabilizing	0.824	D	0.703	prob.neutral	None	None	None	None	N
E/Q	0.1659	likely_benign	0.1525	benign	-0.721	Destabilizing	0.973	D	0.58	neutral	D	0.522765193	None	None	N
E/R	0.3625	ambiguous	0.3255	benign	-0.097	Destabilizing	0.985	D	0.619	neutral	None	None	None	None	N
E/S	0.2239	likely_benign	0.2002	benign	-1.096	Destabilizing	0.836	D	0.547	neutral	None	None	None	None	N
E/T	0.2093	likely_benign	0.1871	benign	-0.82	Destabilizing	0.876	D	0.615	neutral	None	None	None	None	N
E/V	0.1753	likely_benign	0.1519	benign	-0.198	Destabilizing	0.031	N	0.372	neutral	N	0.500928483	None	None	N
E/W	0.9139	likely_pathogenic	0.8773	pathogenic	-0.053	Destabilizing	1.0	D	0.697	prob.neutral	None	None	None	None	N
E/Y	0.6298	likely_pathogenic	0.5592	ambiguous	-0.063	Destabilizing	0.998	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.