TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2884	8875;8876;8877	chr2:178769931;178769930;178769929	chr2:179634658;179634657;179634656
N2AB	2884	8875;8876;8877	chr2:178769931;178769930;178769929	chr2:179634658;179634657;179634656
N2A	2884	8875;8876;8877	chr2:178769931;178769930;178769929	chr2:179634658;179634657;179634656
N2B	2838	8737;8738;8739	chr2:178769931;178769930;178769929	chr2:179634658;179634657;179634656
Novex-1	2838	8737;8738;8739	chr2:178769931;178769930;178769929	chr2:179634658;179634657;179634656
Novex-2	2838	8737;8738;8739	chr2:178769931;178769930;178769929	chr2:179634658;179634657;179634656
Novex-3	2884	8875;8876;8877	chr2:178769931;178769930;178769929	chr2:179634658;179634657;179634656

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Ig-19
• Domain position: 3
• Structural Position: 3
• Q(SASA): 0.1311
• 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	rs1390184716	-1.333	0.198	N	0.245	0.22	0.514923749907	gnomAD-2.1.1	3.99E-06	None	None	None	None	N	None	0	2.89E-05	None	0	0	None	0	None	0	0	0
I/V	rs1390184716	-1.333	0.198	N	0.245	0.22	0.514923749907	gnomAD-4.0.0	2.05224E-06	None	None	None	None	N	None	0	2.23644E-05	None	0	0	None	0	0	1.79859E-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
I/A	0.9335	likely_pathogenic	0.9546	pathogenic	-2.062	Highly Destabilizing	0.983	D	0.551	neutral	None	None	None	None	N
I/C	0.9369	likely_pathogenic	0.9634	pathogenic	-1.193	Destabilizing	1.0	D	0.603	neutral	None	None	None	None	N
I/D	0.9956	likely_pathogenic	0.9972	pathogenic	-2.112	Highly Destabilizing	0.999	D	0.707	prob.neutral	None	None	None	None	N
I/E	0.9899	likely_pathogenic	0.9933	pathogenic	-2.092	Highly Destabilizing	0.999	D	0.706	prob.neutral	None	None	None	None	N
I/F	0.5127	ambiguous	0.6071	pathogenic	-1.585	Destabilizing	0.997	D	0.56	neutral	N	0.42133328	None	None	N
I/G	0.988	likely_pathogenic	0.9928	pathogenic	-2.419	Highly Destabilizing	0.999	D	0.691	prob.neutral	None	None	None	None	N
I/H	0.9757	likely_pathogenic	0.9857	pathogenic	-1.771	Destabilizing	1.0	D	0.749	deleterious	None	None	None	None	N
I/K	0.9525	likely_pathogenic	0.9689	pathogenic	-1.432	Destabilizing	0.999	D	0.709	prob.delet.	None	None	None	None	N
I/L	0.3429	ambiguous	0.386	ambiguous	-1.119	Destabilizing	0.798	D	0.495	neutral	N	0.508622859	None	None	N
I/M	0.3405	ambiguous	0.411	ambiguous	-0.743	Destabilizing	0.997	D	0.558	neutral	D	0.604016376	None	None	N
I/N	0.9372	likely_pathogenic	0.9504	pathogenic	-1.284	Destabilizing	0.999	D	0.733	prob.delet.	D	0.647000605	None	None	N
I/P	0.9673	likely_pathogenic	0.9707	pathogenic	-1.406	Destabilizing	0.999	D	0.728	prob.delet.	None	None	None	None	N
I/Q	0.9728	likely_pathogenic	0.9835	pathogenic	-1.481	Destabilizing	0.999	D	0.747	deleterious	None	None	None	None	N
I/R	0.9342	likely_pathogenic	0.9585	pathogenic	-0.822	Destabilizing	0.999	D	0.737	prob.delet.	None	None	None	None	N
I/S	0.9503	likely_pathogenic	0.9678	pathogenic	-1.841	Destabilizing	0.997	D	0.64	neutral	D	0.646173809	None	None	N
I/T	0.9115	likely_pathogenic	0.9319	pathogenic	-1.711	Destabilizing	0.978	D	0.597	neutral	D	0.645698441	None	None	N
I/V	0.1048	likely_benign	0.1104	benign	-1.406	Destabilizing	0.198	N	0.245	neutral	N	0.483756352	None	None	N
I/W	0.9809	likely_pathogenic	0.9893	pathogenic	-1.761	Destabilizing	1.0	D	0.732	prob.delet.	None	None	None	None	N
I/Y	0.9255	likely_pathogenic	0.9537	pathogenic	-1.533	Destabilizing	0.999	D	0.572	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.