TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26795	80608;80609;80610	chr2:178565749;178565748;178565747	chr2:179430476;179430475;179430474
N2AB	25154	75685;75686;75687	chr2:178565749;178565748;178565747	chr2:179430476;179430475;179430474
N2A	24227	72904;72905;72906	chr2:178565749;178565748;178565747	chr2:179430476;179430475;179430474
N2B	17730	53413;53414;53415	chr2:178565749;178565748;178565747	chr2:179430476;179430475;179430474
Novex-1	17855	53788;53789;53790	chr2:178565749;178565748;178565747	chr2:179430476;179430475;179430474
Novex-2	17922	53989;53990;53991	chr2:178565749;178565748;178565747	chr2:179430476;179430475;179430474
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Fn3-83
• Domain position: 16
• Structural Position: 18
• Q(SASA): 0.3851
• 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
T/A	None	None	0.027	N	0.343	0.265	0.226586394389	gnomAD-4.0.0	1.5917E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85935E-06	0	0
T/I	rs777780923	-0.419	0.317	N	0.422	0.275	0.309839678437	gnomAD-4.0.0	1.59169E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43275E-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
T/A	0.0898	likely_benign	0.087	benign	-0.663	Destabilizing	0.027	N	0.343	neutral	N	0.493052027	None	None	N
T/C	0.3918	ambiguous	0.4108	ambiguous	-0.267	Destabilizing	0.824	D	0.391	neutral	None	None	None	None	N
T/D	0.2877	likely_benign	0.2728	benign	-0.092	Destabilizing	0.081	N	0.417	neutral	None	None	None	None	N
T/E	0.272	likely_benign	0.2503	benign	-0.171	Destabilizing	0.081	N	0.32	neutral	None	None	None	None	N
T/F	0.189	likely_benign	0.1857	benign	-1.338	Destabilizing	0.555	D	0.423	neutral	None	None	None	None	N
T/G	0.1994	likely_benign	0.2042	benign	-0.75	Destabilizing	0.081	N	0.338	neutral	None	None	None	None	N
T/H	0.157	likely_benign	0.1565	benign	-1.302	Destabilizing	0.555	D	0.403	neutral	None	None	None	None	N
T/I	0.2039	likely_benign	0.1961	benign	-0.543	Destabilizing	0.317	N	0.422	neutral	N	0.506636832	None	None	N
T/K	0.1398	likely_benign	0.1368	benign	-0.266	Destabilizing	0.002	N	0.179	neutral	None	None	None	None	N
T/L	0.1083	likely_benign	0.1142	benign	-0.543	Destabilizing	0.149	N	0.321	neutral	None	None	None	None	N
T/M	0.0896	likely_benign	0.0881	benign	0.007	Stabilizing	0.791	D	0.392	neutral	None	None	None	None	N
T/N	0.085	likely_benign	0.0801	benign	-0.05	Destabilizing	0.062	N	0.309	neutral	N	0.496415593	None	None	N
T/P	0.5163	ambiguous	0.5021	ambiguous	-0.56	Destabilizing	0.317	N	0.409	neutral	N	0.511916751	None	None	N
T/Q	0.169	likely_benign	0.1603	benign	-0.42	Destabilizing	0.149	N	0.401	neutral	None	None	None	None	N
T/R	0.1212	likely_benign	0.118	benign	-0.048	Destabilizing	None	N	0.143	neutral	None	None	None	None	N
T/S	0.0873	likely_benign	0.0846	benign	-0.262	Destabilizing	None	N	0.144	neutral	N	0.458897354	None	None	N
T/V	0.1655	likely_benign	0.1627	benign	-0.56	Destabilizing	0.149	N	0.314	neutral	None	None	None	None	N
T/W	0.4879	ambiguous	0.5055	ambiguous	-1.274	Destabilizing	0.935	D	0.462	neutral	None	None	None	None	N
T/Y	0.184	likely_benign	0.1938	benign	-0.984	Destabilizing	0.555	D	0.423	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.