TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7771	23536;23537;23538	chr2:178720451;178720450;178720449	chr2:179585178;179585177;179585176
N2AB	7454	22585;22586;22587	chr2:178720451;178720450;178720449	chr2:179585178;179585177;179585176
N2A	6527	19804;19805;19806	chr2:178720451;178720450;178720449	chr2:179585178;179585177;179585176
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-62
• Domain position: 70
• Structural Position: 153
• Q(SASA): 0.4032
• 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	None	None	0.984	N	0.587	0.315	0.370240404367	gnomAD-4.0.0	4.80129E-06	None	None	None	None	N	None	0	0	None	0	2.75482E-04	None	0	0	3.9375E-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	0.1979	likely_benign	0.1871	benign	-1.018	Destabilizing	0.985	D	0.671	neutral	N	0.515935221	None	None	N
E/C	0.8678	likely_pathogenic	0.8607	pathogenic	-0.368	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
E/D	0.0918	likely_benign	0.09	benign	-0.841	Destabilizing	0.894	D	0.554	neutral	N	0.467527985	None	None	N
E/F	0.6731	likely_pathogenic	0.6587	pathogenic	-0.614	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
E/G	0.2689	likely_benign	0.2607	benign	-1.324	Destabilizing	0.999	D	0.739	prob.delet.	N	0.500660394	None	None	N
E/H	0.4749	ambiguous	0.4869	ambiguous	-0.779	Destabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	N
E/I	0.259	likely_benign	0.2377	benign	-0.198	Destabilizing	0.999	D	0.803	deleterious	None	None	None	None	N
E/K	0.2034	likely_benign	0.2089	benign	-0.387	Destabilizing	0.984	D	0.587	neutral	N	0.466525121	None	None	N
E/L	0.3459	ambiguous	0.3305	benign	-0.198	Destabilizing	0.996	D	0.795	deleterious	None	None	None	None	N
E/M	0.4104	ambiguous	0.3851	ambiguous	0.306	Stabilizing	0.999	D	0.779	deleterious	None	None	None	None	N
E/N	0.2113	likely_benign	0.202	benign	-0.819	Destabilizing	0.996	D	0.71	prob.delet.	None	None	None	None	N
E/P	0.6918	likely_pathogenic	0.6708	pathogenic	-0.452	Destabilizing	0.996	D	0.807	deleterious	None	None	None	None	N
E/Q	0.1628	likely_benign	0.1666	benign	-0.73	Destabilizing	0.887	D	0.316	neutral	N	0.478051623	None	None	N
E/R	0.3631	ambiguous	0.3826	ambiguous	-0.146	Destabilizing	0.998	D	0.712	prob.delet.	None	None	None	None	N
E/S	0.2175	likely_benign	0.2104	benign	-1.08	Destabilizing	0.989	D	0.631	neutral	None	None	None	None	N
E/T	0.2154	likely_benign	0.1986	benign	-0.822	Destabilizing	0.999	D	0.783	deleterious	None	None	None	None	N
E/V	0.177	likely_benign	0.1588	benign	-0.452	Destabilizing	0.997	D	0.799	deleterious	N	0.456214914	None	None	N
E/W	0.8811	likely_pathogenic	0.8866	pathogenic	-0.322	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
E/Y	0.5633	ambiguous	0.565	pathogenic	-0.355	Destabilizing	1.0	D	0.799	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.