TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32277	97054;97055;97056	chr2:178543144;178543143;178543142	chr2:179407871;179407870;179407869
N2AB	30636	92131;92132;92133	chr2:178543144;178543143;178543142	chr2:179407871;179407870;179407869
N2A	29709	89350;89351;89352	chr2:178543144;178543143;178543142	chr2:179407871;179407870;179407869
N2B	23212	69859;69860;69861	chr2:178543144;178543143;178543142	chr2:179407871;179407870;179407869
Novex-1	23337	70234;70235;70236	chr2:178543144;178543143;178543142	chr2:179407871;179407870;179407869
Novex-2	23404	70435;70436;70437	chr2:178543144;178543143;178543142	chr2:179407871;179407870;179407869
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATA
• RefSeq wild type template codon: TAT
• Domain: Fn3-123
• Domain position: 76
• Structural Position: 108
• Q(SASA): 0.0578
• 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
I/V	rs2154143314	None	None	N	0.135	0.105	0.237489013734	gnomAD-4.0.0	7.96582E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	7.16538E-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	0.791	likely_pathogenic	0.8043	pathogenic	-3.314	Highly Destabilizing	0.035	N	0.606	neutral	None	None	None	None	N
I/C	0.8783	likely_pathogenic	0.8814	pathogenic	-2.353	Highly Destabilizing	0.824	D	0.737	prob.delet.	None	None	None	None	N
I/D	0.9973	likely_pathogenic	0.9977	pathogenic	-3.683	Highly Destabilizing	0.555	D	0.81	deleterious	None	None	None	None	N
I/E	0.9926	likely_pathogenic	0.9934	pathogenic	-3.403	Highly Destabilizing	0.555	D	0.8	deleterious	None	None	None	None	N
I/F	0.7767	likely_pathogenic	0.7792	pathogenic	-1.939	Destabilizing	0.38	N	0.587	neutral	None	None	None	None	N
I/G	0.9521	likely_pathogenic	0.953	pathogenic	-3.816	Highly Destabilizing	0.262	N	0.783	deleterious	None	None	None	None	N
I/H	0.9947	likely_pathogenic	0.9957	pathogenic	-3.174	Highly Destabilizing	0.935	D	0.861	deleterious	None	None	None	None	N
I/K	0.9924	likely_pathogenic	0.994	pathogenic	-2.651	Highly Destabilizing	0.484	N	0.8	deleterious	N	0.509079141	None	None	N
I/L	0.2618	likely_benign	0.2679	benign	-1.766	Destabilizing	0.005	N	0.289	neutral	N	0.498973108	None	None	N
I/M	0.3971	ambiguous	0.3961	ambiguous	-1.928	Destabilizing	0.317	N	0.563	neutral	D	0.526701214	None	None	N
I/N	0.969	likely_pathogenic	0.9748	pathogenic	-3.271	Highly Destabilizing	0.791	D	0.844	deleterious	None	None	None	None	N
I/P	0.9922	likely_pathogenic	0.993	pathogenic	-2.28	Highly Destabilizing	0.555	D	0.83	deleterious	None	None	None	None	N
I/Q	0.9894	likely_pathogenic	0.9907	pathogenic	-2.989	Highly Destabilizing	0.791	D	0.847	deleterious	None	None	None	None	N
I/R	0.9862	likely_pathogenic	0.9893	pathogenic	-2.473	Highly Destabilizing	0.484	N	0.843	deleterious	N	0.509079141	None	None	N
I/S	0.9211	likely_pathogenic	0.9327	pathogenic	-3.747	Highly Destabilizing	0.149	N	0.742	deleterious	None	None	None	None	N
I/T	0.8871	likely_pathogenic	0.8979	pathogenic	-3.341	Highly Destabilizing	0.062	N	0.588	neutral	N	0.508825651	None	None	N
I/V	0.0729	likely_benign	0.072	benign	-2.28	Highly Destabilizing	None	N	0.135	neutral	N	0.351323519	None	None	N
I/W	0.9956	likely_pathogenic	0.9959	pathogenic	-2.174	Highly Destabilizing	0.935	D	0.834	deleterious	None	None	None	None	N
I/Y	0.971	likely_pathogenic	0.9754	pathogenic	-2.189	Highly Destabilizing	0.555	D	0.708	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.