TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28974	87145;87146;87147	chr2:178558539;178558538;178558537	chr2:179423266;179423265;179423264
N2AB	27333	82222;82223;82224	chr2:178558539;178558538;178558537	chr2:179423266;179423265;179423264
N2A	26406	79441;79442;79443	chr2:178558539;178558538;178558537	chr2:179423266;179423265;179423264
N2B	19909	59950;59951;59952	chr2:178558539;178558538;178558537	chr2:179423266;179423265;179423264
Novex-1	20034	60325;60326;60327	chr2:178558539;178558538;178558537	chr2:179423266;179423265;179423264
Novex-2	20101	60526;60527;60528	chr2:178558539;178558538;178558537	chr2:179423266;179423265;179423264
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: Fn3-99
• Domain position: 33
• Structural Position: 35
• Q(SASA): 0.1585
• 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	rs762434090	-2.484	0.732	N	0.764	0.516	0.789066735824	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.91E-06	0
I/T	rs762434090	-2.484	0.732	N	0.764	0.516	0.789066735824	gnomAD-4.0.0	4.10538E-06	None	None	None	None	I	None	2.98739E-05	0	None	0	0	None	0	0	2.69836E-06	2.31879E-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	0.7653	likely_pathogenic	0.8403	pathogenic	-2.536	Highly Destabilizing	0.858	D	0.659	neutral	None	None	None	None	I
I/C	0.9379	likely_pathogenic	0.9477	pathogenic	-1.566	Destabilizing	0.997	D	0.709	prob.delet.	None	None	None	None	I
I/D	0.9907	likely_pathogenic	0.9929	pathogenic	-2.749	Highly Destabilizing	0.996	D	0.779	deleterious	None	None	None	None	I
I/E	0.9806	likely_pathogenic	0.9852	pathogenic	-2.622	Highly Destabilizing	0.984	D	0.774	deleterious	None	None	None	None	I
I/F	0.7922	likely_pathogenic	0.8483	pathogenic	-1.698	Destabilizing	0.927	D	0.739	prob.delet.	D	0.522397229	None	None	I
I/G	0.9659	likely_pathogenic	0.977	pathogenic	-2.994	Highly Destabilizing	0.988	D	0.765	deleterious	None	None	None	None	I
I/H	0.9802	likely_pathogenic	0.9863	pathogenic	-2.411	Highly Destabilizing	0.998	D	0.757	deleterious	None	None	None	None	I
I/K	0.9762	likely_pathogenic	0.9812	pathogenic	-2.009	Highly Destabilizing	0.716	D	0.775	deleterious	None	None	None	None	I
I/L	0.2519	likely_benign	0.3033	benign	-1.249	Destabilizing	0.024	N	0.497	neutral	N	0.513155914	None	None	I
I/M	0.3211	likely_benign	0.3807	ambiguous	-0.879	Destabilizing	0.792	D	0.697	prob.neutral	N	0.516538333	None	None	I
I/N	0.7901	likely_pathogenic	0.8043	pathogenic	-2.06	Highly Destabilizing	0.995	D	0.79	deleterious	D	0.544050337	None	None	I
I/P	0.8977	likely_pathogenic	0.9284	pathogenic	-1.656	Destabilizing	0.996	D	0.786	deleterious	None	None	None	None	I
I/Q	0.9711	likely_pathogenic	0.9786	pathogenic	-2.091	Highly Destabilizing	0.991	D	0.793	deleterious	None	None	None	None	I
I/R	0.9642	likely_pathogenic	0.9717	pathogenic	-1.474	Destabilizing	0.971	D	0.791	deleterious	None	None	None	None	I
I/S	0.8464	likely_pathogenic	0.8861	pathogenic	-2.677	Highly Destabilizing	0.97	D	0.731	prob.delet.	D	0.543289869	None	None	I
I/T	0.604	likely_pathogenic	0.6444	pathogenic	-2.428	Highly Destabilizing	0.732	D	0.764	deleterious	N	0.509056368	None	None	I
I/V	0.0857	likely_benign	0.0945	benign	-1.656	Destabilizing	None	N	0.271	neutral	N	0.473770806	None	None	I
I/W	0.9911	likely_pathogenic	0.9941	pathogenic	-2.045	Highly Destabilizing	0.999	D	0.731	prob.delet.	None	None	None	None	I
I/Y	0.9599	likely_pathogenic	0.9711	pathogenic	-1.808	Destabilizing	0.8	D	0.755	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.