TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25336	76231;76232;76233	chr2:178570126;178570125;178570124	chr2:179434853;179434852;179434851
N2AB	23695	71308;71309;71310	chr2:178570126;178570125;178570124	chr2:179434853;179434852;179434851
N2A	22768	68527;68528;68529	chr2:178570126;178570125;178570124	chr2:179434853;179434852;179434851
N2B	16271	49036;49037;49038	chr2:178570126;178570125;178570124	chr2:179434853;179434852;179434851
Novex-1	16396	49411;49412;49413	chr2:178570126;178570125;178570124	chr2:179434853;179434852;179434851
Novex-2	16463	49612;49613;49614	chr2:178570126;178570125;178570124	chr2:179434853;179434852;179434851
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: Fn3-72
• Domain position: 33
• Structural Position: 35
• Q(SASA): 0.1559
• 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	rs1707608600	None	1.0	D	0.858	0.562	0.756051586483	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	0	6.56E-05	0	0	0	None	0	0	0	0	0
I/T	rs1707608600	None	1.0	D	0.858	0.562	0.756051586483	gnomAD-4.0.0	2.56322E-06	None	None	None	None	I	None	0	3.39109E-05	None	0	0	None	0	0	0	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	0.9829	likely_pathogenic	0.9829	pathogenic	-2.41	Highly Destabilizing	0.999	D	0.671	neutral	None	None	None	None	I
I/C	0.9786	likely_pathogenic	0.9813	pathogenic	-1.611	Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	I
I/D	0.9976	likely_pathogenic	0.9958	pathogenic	-2.259	Highly Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	I
I/E	0.9957	likely_pathogenic	0.994	pathogenic	-2.134	Highly Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	I
I/F	0.8946	likely_pathogenic	0.8801	pathogenic	-1.544	Destabilizing	1.0	D	0.849	deleterious	D	0.545274424	None	None	I
I/G	0.9962	likely_pathogenic	0.9948	pathogenic	-2.875	Highly Destabilizing	1.0	D	0.874	deleterious	None	None	None	None	I
I/H	0.9954	likely_pathogenic	0.9934	pathogenic	-2.159	Highly Destabilizing	1.0	D	0.856	deleterious	None	None	None	None	I
I/K	0.9911	likely_pathogenic	0.9872	pathogenic	-1.774	Destabilizing	1.0	D	0.878	deleterious	None	None	None	None	I
I/L	0.4216	ambiguous	0.4454	ambiguous	-1.117	Destabilizing	0.993	D	0.436	neutral	N	0.492100521	None	None	I
I/M	0.6008	likely_pathogenic	0.6051	pathogenic	-0.919	Destabilizing	1.0	D	0.836	deleterious	D	0.547809319	None	None	I
I/N	0.9493	likely_pathogenic	0.9132	pathogenic	-1.808	Destabilizing	1.0	D	0.879	deleterious	D	0.560179583	None	None	I
I/P	0.9727	likely_pathogenic	0.9694	pathogenic	-1.523	Destabilizing	1.0	D	0.88	deleterious	None	None	None	None	I
I/Q	0.9941	likely_pathogenic	0.9921	pathogenic	-1.843	Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	I
I/R	0.9893	likely_pathogenic	0.9851	pathogenic	-1.279	Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	I
I/S	0.982	likely_pathogenic	0.9781	pathogenic	-2.519	Highly Destabilizing	1.0	D	0.869	deleterious	D	0.559419114	None	None	I
I/T	0.9696	likely_pathogenic	0.9704	pathogenic	-2.262	Highly Destabilizing	1.0	D	0.858	deleterious	D	0.525185614	None	None	I
I/V	0.1573	likely_benign	0.2184	benign	-1.523	Destabilizing	0.993	D	0.409	neutral	N	0.505555151	None	None	I
I/W	0.9971	likely_pathogenic	0.9954	pathogenic	-1.789	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	I
I/Y	0.9787	likely_pathogenic	0.9711	pathogenic	-1.552	Destabilizing	1.0	D	0.883	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.