TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3851	11776;11777;11778	chr2:178741682;178741681;178741680	chr2:179606409;179606408;179606407
N2AB	3534	10825;10826;10827	chr2:178741682;178741681;178741680	chr2:179606409;179606408;179606407
N2A	None	None	chr2:None	chr2:None
N2B	3488	10687;10688;10689	chr2:178741682;178741681;178741680	chr2:179606409;179606408;179606407
Novex-1	3613	11062;11063;11064	chr2:178741682;178741681;178741680	chr2:179606409;179606408;179606407
Novex-2	3680	11263;11264;11265	chr2:178741682;178741681;178741680	chr2:179606409;179606408;179606407
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Ig-27
• Domain position: 32
• Structural Position: 46
• Q(SASA): 0.1218
• Predicted PPI site: I

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
I/T	None	None	0.338	D	0.733	0.535	None	gnomAD-4.0.0	5.47367E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	3.59793E-06	4.63736E-05	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
I/A	0.8311	likely_pathogenic	0.8247	pathogenic	-2.161	Highly Destabilizing	0.218	N	0.717	prob.delet.	None	None	None	None	I
I/C	0.876	likely_pathogenic	0.8856	pathogenic	-1.096	Destabilizing	0.973	D	0.774	deleterious	None	None	None	None	I
I/D	0.9728	likely_pathogenic	0.9806	pathogenic	-2.007	Highly Destabilizing	0.906	D	0.86	deleterious	None	None	None	None	I
I/E	0.9292	likely_pathogenic	0.9433	pathogenic	-1.929	Destabilizing	0.906	D	0.835	deleterious	None	None	None	None	I
I/F	0.3462	ambiguous	0.3462	ambiguous	-1.447	Destabilizing	0.782	D	0.708	prob.delet.	D	0.619698062	None	None	I
I/G	0.9408	likely_pathogenic	0.9449	pathogenic	-2.556	Highly Destabilizing	0.906	D	0.813	deleterious	None	None	None	None	I
I/H	0.9057	likely_pathogenic	0.9245	pathogenic	-1.798	Destabilizing	0.991	D	0.853	deleterious	None	None	None	None	I
I/K	0.8241	likely_pathogenic	0.8648	pathogenic	-1.584	Destabilizing	0.906	D	0.841	deleterious	None	None	None	None	I
I/L	0.2149	likely_benign	0.2197	benign	-1.086	Destabilizing	0.084	N	0.419	neutral	D	0.577958716	None	None	I
I/M	0.1984	likely_benign	0.2006	benign	-0.747	Destabilizing	0.782	D	0.691	prob.neutral	D	0.654502453	None	None	I
I/N	0.7314	likely_pathogenic	0.774	pathogenic	-1.446	Destabilizing	0.957	D	0.864	deleterious	D	0.731375063	None	None	I
I/P	0.9213	likely_pathogenic	0.9345	pathogenic	-1.42	Destabilizing	0.967	D	0.863	deleterious	None	None	None	None	I
I/Q	0.8687	likely_pathogenic	0.8974	pathogenic	-1.552	Destabilizing	0.967	D	0.857	deleterious	None	None	None	None	I
I/R	0.7794	likely_pathogenic	0.832	pathogenic	-1.024	Destabilizing	0.906	D	0.864	deleterious	None	None	None	None	I
I/S	0.772	likely_pathogenic	0.7939	pathogenic	-2.024	Highly Destabilizing	0.782	D	0.822	deleterious	D	0.767328348	None	None	I
I/T	0.6704	likely_pathogenic	0.6881	pathogenic	-1.827	Destabilizing	0.338	N	0.733	prob.delet.	D	0.647396739	None	None	I
I/V	0.1365	likely_benign	0.1225	benign	-1.42	Destabilizing	None	N	0.235	neutral	N	0.470406626	None	None	I
I/W	0.9369	likely_pathogenic	0.9493	pathogenic	-1.624	Destabilizing	0.991	D	0.859	deleterious	None	None	None	None	I
I/Y	0.7685	likely_pathogenic	0.8032	pathogenic	-1.413	Destabilizing	0.906	D	0.783	deleterious	None	None	None	None	I

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.