TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14725	44398;44399;44400	chr2:178630349;178630348;178630347	chr2:179495076;179495075;179495074
N2AB	13084	39475;39476;39477	chr2:178630349;178630348;178630347	chr2:179495076;179495075;179495074
N2A	12157	36694;36695;36696	chr2:178630349;178630348;178630347	chr2:179495076;179495075;179495074
N2B	5660	17203;17204;17205	chr2:178630349;178630348;178630347	chr2:179495076;179495075;179495074
Novex-1	5785	17578;17579;17580	chr2:178630349;178630348;178630347	chr2:179495076;179495075;179495074
Novex-2	5852	17779;17780;17781	chr2:178630349;178630348;178630347	chr2:179495076;179495075;179495074
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-98
• Domain position: 51
• Structural Position: 130
• Q(SASA): 0.7147
• 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/G	None	None	0.999	N	0.643	0.394	0.309530620856	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
E/A	0.1636	likely_benign	0.1618	benign	-0.204	Destabilizing	0.996	D	0.685	prob.delet.	N	0.51589602	None	None	N
E/C	0.8469	likely_pathogenic	0.8653	pathogenic	-0.095	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
E/D	0.1391	likely_benign	0.132	benign	-0.248	Destabilizing	0.262	N	0.263	neutral	N	0.422485279	None	None	N
E/F	0.6758	likely_pathogenic	0.6833	pathogenic	-0.062	Destabilizing	1.0	D	0.798	deleterious	None	None	None	None	N
E/G	0.1988	likely_benign	0.197	benign	-0.378	Destabilizing	0.999	D	0.643	neutral	N	0.474591958	None	None	N
E/H	0.4517	ambiguous	0.4864	ambiguous	0.325	Stabilizing	1.0	D	0.767	deleterious	None	None	None	None	N
E/I	0.2903	likely_benign	0.3045	benign	0.212	Stabilizing	1.0	D	0.821	deleterious	None	None	None	None	N
E/K	0.1348	likely_benign	0.1437	benign	0.47	Stabilizing	0.996	D	0.622	neutral	N	0.431628313	None	None	N
E/L	0.4579	ambiguous	0.462	ambiguous	0.212	Stabilizing	1.0	D	0.767	deleterious	None	None	None	None	N
E/M	0.4425	ambiguous	0.4471	ambiguous	0.136	Stabilizing	1.0	D	0.782	deleterious	None	None	None	None	N
E/N	0.2459	likely_benign	0.2511	benign	0.067	Stabilizing	0.998	D	0.776	deleterious	None	None	None	None	N
E/P	0.909	likely_pathogenic	0.9209	pathogenic	0.093	Stabilizing	1.0	D	0.766	deleterious	None	None	None	None	N
E/Q	0.1537	likely_benign	0.1668	benign	0.118	Stabilizing	0.999	D	0.739	deleterious	N	0.44004705	None	None	N
E/R	0.2511	likely_benign	0.2716	benign	0.684	Stabilizing	0.999	D	0.754	deleterious	None	None	None	None	N
E/S	0.2176	likely_benign	0.218	benign	-0.055	Destabilizing	0.993	D	0.651	prob.neutral	None	None	None	None	N
E/T	0.2059	likely_benign	0.2094	benign	0.097	Stabilizing	0.999	D	0.765	deleterious	None	None	None	None	N
E/V	0.1768	likely_benign	0.1832	benign	0.093	Stabilizing	1.0	D	0.736	deleterious	N	0.455574726	None	None	N
E/W	0.8549	likely_pathogenic	0.8588	pathogenic	0.071	Stabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
E/Y	0.5752	likely_pathogenic	0.5969	pathogenic	0.181	Stabilizing	1.0	D	0.763	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.