TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25767	77524;77525;77526	chr2:178568833;178568832;178568831	chr2:179433560;179433559;179433558
N2AB	24126	72601;72602;72603	chr2:178568833;178568832;178568831	chr2:179433560;179433559;179433558
N2A	23199	69820;69821;69822	chr2:178568833;178568832;178568831	chr2:179433560;179433559;179433558
N2B	16702	50329;50330;50331	chr2:178568833;178568832;178568831	chr2:179433560;179433559;179433558
Novex-1	16827	50704;50705;50706	chr2:178568833;178568832;178568831	chr2:179433560;179433559;179433558
Novex-2	16894	50905;50906;50907	chr2:178568833;178568832;178568831	chr2:179433560;179433559;179433558
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Fn3-75
• Domain position: 70
• Structural Position: 104
• Q(SASA): 0.0914
• 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
Y/N	rs1303024823	None	0.996	D	0.878	0.858	0.94193011176	gnomAD-4.0.0	2.73781E-06	None	None	None	None	N	None	0	0	None	0	2.52334E-05	None	0	0	0	0	4.97117E-05

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
Y/A	0.9912	likely_pathogenic	0.9904	pathogenic	-3.102	Highly Destabilizing	0.979	D	0.85	deleterious	None	None	None	None	N
Y/C	0.9229	likely_pathogenic	0.9024	pathogenic	-1.918	Destabilizing	1.0	D	0.856	deleterious	D	0.649022935	None	None	N
Y/D	0.9937	likely_pathogenic	0.9941	pathogenic	-3.356	Highly Destabilizing	0.996	D	0.9	deleterious	D	0.681293822	None	None	N
Y/E	0.9978	likely_pathogenic	0.9978	pathogenic	-3.165	Highly Destabilizing	0.998	D	0.874	deleterious	None	None	None	None	N
Y/F	0.2838	likely_benign	0.2242	benign	-1.134	Destabilizing	0.981	D	0.734	prob.delet.	D	0.612381999	None	None	N
Y/G	0.9791	likely_pathogenic	0.9802	pathogenic	-3.515	Highly Destabilizing	0.226	N	0.69	prob.neutral	None	None	None	None	N
Y/H	0.958	likely_pathogenic	0.9442	pathogenic	-2.011	Highly Destabilizing	0.998	D	0.785	deleterious	D	0.665274461	None	None	N
Y/I	0.9368	likely_pathogenic	0.9365	pathogenic	-1.734	Destabilizing	0.987	D	0.826	deleterious	None	None	None	None	N
Y/K	0.9956	likely_pathogenic	0.9955	pathogenic	-2.3	Highly Destabilizing	0.975	D	0.873	deleterious	None	None	None	None	N
Y/L	0.8938	likely_pathogenic	0.8976	pathogenic	-1.734	Destabilizing	0.88	D	0.822	deleterious	None	None	None	None	N
Y/M	0.9557	likely_pathogenic	0.9489	pathogenic	-1.44	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
Y/N	0.942	likely_pathogenic	0.9382	pathogenic	-3.052	Highly Destabilizing	0.996	D	0.878	deleterious	D	0.681092018	None	None	N
Y/P	0.9992	likely_pathogenic	0.9992	pathogenic	-2.204	Highly Destabilizing	1.0	D	0.889	deleterious	None	None	None	None	N
Y/Q	0.9959	likely_pathogenic	0.9949	pathogenic	-2.829	Highly Destabilizing	0.998	D	0.827	deleterious	None	None	None	None	N
Y/R	0.9914	likely_pathogenic	0.9904	pathogenic	-1.996	Destabilizing	0.996	D	0.878	deleterious	None	None	None	None	N
Y/S	0.9805	likely_pathogenic	0.9791	pathogenic	-3.427	Highly Destabilizing	0.996	D	0.85	deleterious	D	0.681293822	None	None	N
Y/T	0.9902	likely_pathogenic	0.9896	pathogenic	-3.119	Highly Destabilizing	0.998	D	0.874	deleterious	None	None	None	None	N
Y/V	0.9007	likely_pathogenic	0.9013	pathogenic	-2.204	Highly Destabilizing	0.998	D	0.814	deleterious	None	None	None	None	N
Y/W	0.9014	likely_pathogenic	0.8805	pathogenic	-0.496	Destabilizing	1.0	D	0.773	deleterious	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.