TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7648	23167;23168;23169	chr2:178721077;178721076;178721075	chr2:179585804;179585803;179585802
N2AB	7331	22216;22217;22218	chr2:178721077;178721076;178721075	chr2:179585804;179585803;179585802
N2A	6404	19435;19436;19437	chr2:178721077;178721076;178721075	chr2:179585804;179585803;179585802
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-61
• Domain position: 41
• Structural Position: 56
• Q(SASA): 0.4721
• 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	rs397517502	-0.001	0.079	N	0.207	0.237	0.314417295294	gnomAD-2.1.1	2.86E-05	None	None	None	None	N	None	4.14E-05	2.83E-05	None	0	0	None	6.54E-05	None	0	3.13E-05	0
E/K	rs397517502	-0.001	0.079	N	0.207	0.237	0.314417295294	gnomAD-3.1.2	3.29E-05	None	None	None	None	N	None	4.83E-05	0	0	0	0	None	0	0	4.41E-05	0	0
E/K	rs397517502	-0.001	0.079	N	0.207	0.237	0.314417295294	1000 genomes	1.99681E-04	None	None	None	None	N	None	8E-04	0	None	None	0	0	None	None	None	0	None
E/K	rs397517502	-0.001	0.079	N	0.207	0.237	0.314417295294	gnomAD-4.0.0	1.48778E-05	None	None	None	None	N	None	6.66649E-05	1.66694E-05	None	0	0	None	0	0	1.27196E-05	2.19732E-05	1.60149E-05

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	0.1244	likely_benign	0.151	benign	-0.819	Destabilizing	0.002	N	0.256	neutral	D	0.526517574	None	None	N
E/C	0.8395	likely_pathogenic	0.8811	pathogenic	-0.427	Destabilizing	0.985	D	0.513	neutral	None	None	None	None	N
E/D	0.295	likely_benign	0.341	ambiguous	-0.622	Destabilizing	None	N	0.219	neutral	N	0.489656029	None	None	N
E/F	0.7081	likely_pathogenic	0.783	pathogenic	-0.213	Destabilizing	0.915	D	0.484	neutral	None	None	None	None	N
E/G	0.2311	likely_benign	0.3047	benign	-1.113	Destabilizing	0.506	D	0.373	neutral	N	0.505041714	None	None	N
E/H	0.4501	ambiguous	0.5281	ambiguous	-0.045	Destabilizing	0.989	D	0.389	neutral	None	None	None	None	N
E/I	0.2423	likely_benign	0.2854	benign	-0.033	Destabilizing	0.554	D	0.434	neutral	None	None	None	None	N
E/K	0.0875	likely_benign	0.1059	benign	-0.153	Destabilizing	0.079	N	0.207	neutral	N	0.485073596	None	None	N
E/L	0.2596	likely_benign	0.2999	benign	-0.033	Destabilizing	0.261	N	0.402	neutral	None	None	None	None	N
E/M	0.3339	likely_benign	0.3784	ambiguous	0.171	Stabilizing	0.772	D	0.465	neutral	None	None	None	None	N
E/N	0.399	ambiguous	0.4844	ambiguous	-0.731	Destabilizing	0.535	D	0.366	neutral	None	None	None	None	N
E/P	0.2955	likely_benign	0.3595	ambiguous	-0.275	Destabilizing	0.427	N	0.411	neutral	None	None	None	None	N
E/Q	0.1042	likely_benign	0.1185	benign	-0.631	Destabilizing	0.879	D	0.403	neutral	D	0.532539469	None	None	N
E/R	0.1665	likely_benign	0.2099	benign	0.257	Stabilizing	0.726	D	0.367	neutral	None	None	None	None	N
E/S	0.257	likely_benign	0.3201	benign	-0.95	Destabilizing	0.289	N	0.323	neutral	None	None	None	None	N
E/T	0.2419	likely_benign	0.3024	benign	-0.698	Destabilizing	0.529	D	0.381	neutral	None	None	None	None	N
E/V	0.1409	likely_benign	0.1652	benign	-0.275	Destabilizing	0.003	N	0.253	neutral	D	0.536638567	None	None	N
E/W	0.9042	likely_pathogenic	0.9403	pathogenic	0.125	Stabilizing	0.997	D	0.595	neutral	None	None	None	None	N
E/Y	0.6343	likely_pathogenic	0.7152	pathogenic	0.066	Stabilizing	0.989	D	0.477	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.