TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29432	88519;88520;88521	chr2:178556860;178556859;178556858	chr2:179421587;179421586;179421585
N2AB	27791	83596;83597;83598	chr2:178556860;178556859;178556858	chr2:179421587;179421586;179421585
N2A	26864	80815;80816;80817	chr2:178556860;178556859;178556858	chr2:179421587;179421586;179421585
N2B	20367	61324;61325;61326	chr2:178556860;178556859;178556858	chr2:179421587;179421586;179421585
Novex-1	20492	61699;61700;61701	chr2:178556860;178556859;178556858	chr2:179421587;179421586;179421585
Novex-2	20559	61900;61901;61902	chr2:178556860;178556859;178556858	chr2:179421587;179421586;179421585
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Fn3-102
• Domain position: 98
• Structural Position: 131
• Q(SASA): 0.5798
• 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
I/V	rs775025065	-0.268	None	N	0.06	0.058	None	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.9E-06	0
I/V	rs775025065	-0.268	None	N	0.06	0.058	None	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
I/V	rs775025065	-0.268	None	N	0.06	0.058	None	gnomAD-4.0.0	5.57805E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	7.45884E-05	0	3.20236E-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
I/A	0.204	likely_benign	0.1485	benign	-1.248	Destabilizing	0.029	N	0.341	neutral	None	None	None	None	N
I/C	0.5841	likely_pathogenic	0.521	ambiguous	-0.806	Destabilizing	0.703	D	0.453	neutral	None	None	None	None	N
I/D	0.6561	likely_pathogenic	0.5429	ambiguous	-0.841	Destabilizing	0.703	D	0.646	neutral	None	None	None	None	N
I/E	0.4271	ambiguous	0.3347	benign	-0.913	Destabilizing	0.25	N	0.571	neutral	None	None	None	None	N
I/F	0.1914	likely_benign	0.1445	benign	-1.184	Destabilizing	0.468	N	0.384	neutral	N	0.445220689	None	None	N
I/G	0.55	ambiguous	0.4429	ambiguous	-1.475	Destabilizing	0.403	N	0.553	neutral	None	None	None	None	N
I/H	0.425	ambiguous	0.3504	ambiguous	-0.722	Destabilizing	0.878	D	0.535	neutral	None	None	None	None	N
I/K	0.2301	likely_benign	0.1886	benign	-0.666	Destabilizing	0.143	N	0.553	neutral	None	None	None	None	N
I/L	0.1119	likely_benign	0.1008	benign	-0.744	Destabilizing	0.022	N	0.225	neutral	N	0.42532542	None	None	N
I/M	0.0866	likely_benign	0.0775	benign	-0.475	Destabilizing	0.691	D	0.479	neutral	N	0.427059003	None	None	N
I/N	0.2802	likely_benign	0.2149	benign	-0.431	Destabilizing	0.641	D	0.641	neutral	N	0.445914122	None	None	N
I/P	0.8575	likely_pathogenic	0.7949	pathogenic	-0.879	Destabilizing	0.878	D	0.654	prob.neutral	None	None	None	None	N
I/Q	0.2776	likely_benign	0.2366	benign	-0.736	Destabilizing	0.538	D	0.664	prob.neutral	None	None	None	None	N
I/R	0.177	likely_benign	0.1433	benign	-0.021	Destabilizing	0.001	N	0.267	neutral	None	None	None	None	N
I/S	0.2099	likely_benign	0.1589	benign	-0.962	Destabilizing	0.201	N	0.521	neutral	N	0.415417857	None	None	N
I/T	0.0994	likely_benign	0.077	benign	-0.927	Destabilizing	0.094	N	0.425	neutral	N	0.382998794	None	None	N
I/V	0.0714	likely_benign	0.064	benign	-0.879	Destabilizing	None	N	0.06	neutral	N	0.382921437	None	None	N
I/W	0.7493	likely_pathogenic	0.6915	pathogenic	-1.169	Destabilizing	0.964	D	0.567	neutral	None	None	None	None	N
I/Y	0.5516	ambiguous	0.4691	ambiguous	-0.916	Destabilizing	0.703	D	0.587	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.