TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2099	6520;6521;6522	chr2:178775569;178775568;178775567	chr2:179640296;179640295;179640294
N2AB	2099	6520;6521;6522	chr2:178775569;178775568;178775567	chr2:179640296;179640295;179640294
N2A	2099	6520;6521;6522	chr2:178775569;178775568;178775567	chr2:179640296;179640295;179640294
N2B	2053	6382;6383;6384	chr2:178775569;178775568;178775567	chr2:179640296;179640295;179640294
Novex-1	2053	6382;6383;6384	chr2:178775569;178775568;178775567	chr2:179640296;179640295;179640294
Novex-2	2053	6382;6383;6384	chr2:178775569;178775568;178775567	chr2:179640296;179640295;179640294
Novex-3	2099	6520;6521;6522	chr2:178775569;178775568;178775567	chr2:179640296;179640295;179640294

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Ig-10
• Domain position: 22
• Structural Position: 33
• Q(SASA): 0.1082
• 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
V/F	rs1055695339	None	0.82	D	0.817	0.614	None	gnomAD-3.1.2	1.97E-05	None	None	None	None	N	None	7.24E-05	0	0	0	0	None	0	0	0	0	0
V/F	rs1055695339	None	0.82	D	0.817	0.614	None	gnomAD-4.0.0	1.97182E-05	None	None	None	None	N	None	7.23798E-05	0	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
V/A	0.8325	likely_pathogenic	0.858	pathogenic	-2.287	Highly Destabilizing	0.517	D	0.682	prob.neutral	N	0.503881984	None	None	N
V/C	0.8893	likely_pathogenic	0.8976	pathogenic	-1.651	Destabilizing	0.054	N	0.681	prob.neutral	None	None	None	None	N
V/D	0.9987	likely_pathogenic	0.999	pathogenic	-3.296	Highly Destabilizing	0.983	D	0.89	deleterious	D	0.683986142	None	None	N
V/E	0.9954	likely_pathogenic	0.9962	pathogenic	-3.03	Highly Destabilizing	0.961	D	0.855	deleterious	None	None	None	None	N
V/F	0.9127	likely_pathogenic	0.9385	pathogenic	-1.355	Destabilizing	0.82	D	0.817	deleterious	D	0.684728904	None	None	N
V/G	0.8958	likely_pathogenic	0.9156	pathogenic	-2.827	Highly Destabilizing	0.949	D	0.877	deleterious	D	0.581337849	None	None	N
V/H	0.9988	likely_pathogenic	0.9991	pathogenic	-2.699	Highly Destabilizing	0.996	D	0.892	deleterious	None	None	None	None	N
V/I	0.1557	likely_benign	0.1701	benign	-0.736	Destabilizing	0.034	N	0.353	neutral	D	0.593814737	None	None	N
V/K	0.9979	likely_pathogenic	0.9981	pathogenic	-1.993	Destabilizing	0.961	D	0.851	deleterious	None	None	None	None	N
V/L	0.5079	ambiguous	0.6257	pathogenic	-0.736	Destabilizing	0.008	N	0.403	neutral	D	0.624314152	None	None	N
V/M	0.7133	likely_pathogenic	0.7719	pathogenic	-0.808	Destabilizing	0.923	D	0.673	neutral	None	None	None	None	N
V/N	0.9937	likely_pathogenic	0.9949	pathogenic	-2.495	Highly Destabilizing	0.987	D	0.885	deleterious	None	None	None	None	N
V/P	0.9985	likely_pathogenic	0.9987	pathogenic	-1.233	Destabilizing	0.987	D	0.853	deleterious	None	None	None	None	N
V/Q	0.9945	likely_pathogenic	0.9955	pathogenic	-2.256	Highly Destabilizing	0.987	D	0.875	deleterious	None	None	None	None	N
V/R	0.9958	likely_pathogenic	0.9965	pathogenic	-1.865	Destabilizing	0.961	D	0.881	deleterious	None	None	None	None	N
V/S	0.9625	likely_pathogenic	0.9689	pathogenic	-2.992	Highly Destabilizing	0.961	D	0.831	deleterious	None	None	None	None	N
V/T	0.8866	likely_pathogenic	0.9038	pathogenic	-2.596	Highly Destabilizing	0.775	D	0.732	prob.delet.	None	None	None	None	N
V/W	0.9993	likely_pathogenic	0.9995	pathogenic	-1.996	Destabilizing	0.996	D	0.879	deleterious	None	None	None	None	N
V/Y	0.9946	likely_pathogenic	0.9963	pathogenic	-1.628	Destabilizing	0.961	D	0.799	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.