TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26431	79516;79517;79518	chr2:178566841;178566840;178566839	chr2:179431568;179431567;179431566
N2AB	24790	74593;74594;74595	chr2:178566841;178566840;178566839	chr2:179431568;179431567;179431566
N2A	23863	71812;71813;71814	chr2:178566841;178566840;178566839	chr2:179431568;179431567;179431566
N2B	17366	52321;52322;52323	chr2:178566841;178566840;178566839	chr2:179431568;179431567;179431566
Novex-1	17491	52696;52697;52698	chr2:178566841;178566840;178566839	chr2:179431568;179431567;179431566
Novex-2	17558	52897;52898;52899	chr2:178566841;178566840;178566839	chr2:179431568;179431567;179431566
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: Fn3-80
• Domain position: 46
• Structural Position: 63
• Q(SASA): 0.8302
• 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/F	None	None	0.967	N	0.651	0.229	0.516437024119	gnomAD-4.0.0	2.40067E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.62503E-06	0	0
I/N	None	None	0.994	N	0.668	0.529	0.72833840645	gnomAD-4.0.0	1.59199E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85902E-06	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	0.6631	likely_pathogenic	0.5387	ambiguous	-0.533	Destabilizing	0.845	D	0.609	neutral	None	None	None	None	I
I/C	0.802	likely_pathogenic	0.7459	pathogenic	-0.975	Destabilizing	0.999	D	0.67	neutral	None	None	None	None	I
I/D	0.9283	likely_pathogenic	0.9061	pathogenic	-0.122	Destabilizing	0.996	D	0.661	neutral	None	None	None	None	I
I/E	0.8701	likely_pathogenic	0.8334	pathogenic	-0.204	Destabilizing	0.987	D	0.665	neutral	None	None	None	None	I
I/F	0.282	likely_benign	0.2209	benign	-0.686	Destabilizing	0.967	D	0.651	neutral	N	0.512419621	None	None	I
I/G	0.8107	likely_pathogenic	0.7276	pathogenic	-0.606	Destabilizing	0.987	D	0.663	neutral	None	None	None	None	I
I/H	0.7873	likely_pathogenic	0.7486	pathogenic	-0.011	Destabilizing	0.999	D	0.667	neutral	None	None	None	None	I
I/K	0.7642	likely_pathogenic	0.7206	pathogenic	-0.419	Destabilizing	0.987	D	0.662	neutral	None	None	None	None	I
I/L	0.1367	likely_benign	0.1165	benign	-0.448	Destabilizing	0.426	N	0.553	neutral	N	0.397883394	None	None	I
I/M	0.1599	likely_benign	0.1189	benign	-0.75	Destabilizing	0.983	D	0.648	neutral	N	0.431361249	None	None	I
I/N	0.5296	ambiguous	0.4496	ambiguous	-0.337	Destabilizing	0.994	D	0.668	neutral	N	0.435380203	None	None	I
I/P	0.8068	likely_pathogenic	0.7914	pathogenic	-0.452	Destabilizing	0.996	D	0.669	neutral	None	None	None	None	I
I/Q	0.7088	likely_pathogenic	0.6566	pathogenic	-0.463	Destabilizing	0.996	D	0.659	neutral	None	None	None	None	I
I/R	0.7107	likely_pathogenic	0.668	pathogenic	-0.032	Destabilizing	0.987	D	0.665	neutral	None	None	None	None	I
I/S	0.5666	likely_pathogenic	0.4862	ambiguous	-0.738	Destabilizing	0.983	D	0.619	neutral	N	0.430859817	None	None	I
I/T	0.5656	likely_pathogenic	0.4499	ambiguous	-0.725	Destabilizing	0.892	D	0.595	neutral	N	0.413620851	None	None	I
I/V	0.1053	likely_benign	0.0839	benign	-0.452	Destabilizing	0.011	N	0.371	neutral	N	0.397344676	None	None	I
I/W	0.8809	likely_pathogenic	0.8516	pathogenic	-0.69	Destabilizing	0.999	D	0.707	prob.neutral	None	None	None	None	I
I/Y	0.7095	likely_pathogenic	0.6597	pathogenic	-0.493	Destabilizing	0.987	D	0.647	neutral	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.