TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22569	67930;67931;67932	chr2:178579325;178579324;178579323	chr2:179444052;179444051;179444050
N2AB	20928	63007;63008;63009	chr2:178579325;178579324;178579323	chr2:179444052;179444051;179444050
N2A	20001	60226;60227;60228	chr2:178579325;178579324;178579323	chr2:179444052;179444051;179444050
N2B	13504	40735;40736;40737	chr2:178579325;178579324;178579323	chr2:179444052;179444051;179444050
Novex-1	13629	41110;41111;41112	chr2:178579325;178579324;178579323	chr2:179444052;179444051;179444050
Novex-2	13696	41311;41312;41313	chr2:178579325;178579324;178579323	chr2:179444052;179444051;179444050
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: CGG
• RefSeq wild type template codon: GCC
• Domain: Ig-127
• Domain position: 10
• Structural Position: 29
• Q(SASA): 0.5868
• 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
R/Q	rs185620750	-0.035	0.997	N	0.597	0.274	None	gnomAD-2.1.1	1.62599E-04	None	None	None	None	I	None	6.47E-05	9.62324E-04	None	0	1.68388E-04	None	6.61E-05	None	0	0	1.6728E-04
R/Q	rs185620750	-0.035	0.997	N	0.597	0.274	None	gnomAD-3.1.2	2.82876E-04	None	None	None	None	I	None	2.41E-05	2.62261E-03	0	0	3.87597E-04	None	0	0	0	0	0
R/Q	rs185620750	-0.035	0.997	N	0.597	0.274	None	1000 genomes	1.99681E-04	None	None	None	None	I	None	0	1.4E-03	None	None	0	0	None	None	None	0	None
R/Q	rs185620750	-0.035	0.997	N	0.597	0.274	None	gnomAD-4.0.0	7.40089E-05	None	None	None	None	I	None	2.67401E-05	1.28849E-03	None	0	2.46316E-04	None	0	0	2.20982E-05	2.20361E-05	1.60705E-05
R/W	rs746313264	-0.317	1.0	N	0.683	0.411	None	gnomAD-2.1.1	3.97E-05	None	None	None	None	I	None	2.48488E-04	0	None	0	2.06825E-04	None	0	None	0	7.86E-06	0
R/W	rs746313264	-0.317	1.0	N	0.683	0.411	None	gnomAD-3.1.2	5.26E-05	None	None	None	None	I	None	1.20668E-04	6.56E-05	0	0	1.93798E-04	None	0	0	1.47E-05	0	0
R/W	rs746313264	-0.317	1.0	N	0.683	0.411	None	gnomAD-4.0.0	3.04839E-05	None	None	None	None	I	None	2.14242E-04	1.67471E-05	None	0	6.71862E-05	None	0	0	2.21002E-05	2.20371E-05	1.60777E-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
R/A	0.6338	likely_pathogenic	0.5402	ambiguous	-0.237	Destabilizing	0.953	D	0.537	neutral	None	None	None	None	I
R/C	0.1937	likely_benign	0.165	benign	-0.267	Destabilizing	0.999	D	0.689	prob.neutral	None	None	None	None	I
R/D	0.8626	likely_pathogenic	0.7964	pathogenic	0.045	Stabilizing	0.986	D	0.621	neutral	None	None	None	None	I
R/E	0.5817	likely_pathogenic	0.495	ambiguous	0.166	Stabilizing	0.953	D	0.532	neutral	None	None	None	None	I
R/F	0.6744	likely_pathogenic	0.582	pathogenic	-0.113	Destabilizing	0.993	D	0.696	prob.neutral	None	None	None	None	I
R/G	0.5902	likely_pathogenic	0.5122	ambiguous	-0.532	Destabilizing	0.975	D	0.546	neutral	N	0.488622168	None	None	I
R/H	0.1045	likely_benign	0.0931	benign	-1.001	Destabilizing	0.128	N	0.424	neutral	None	None	None	None	I
R/I	0.3639	ambiguous	0.2999	benign	0.536	Stabilizing	0.993	D	0.698	prob.neutral	None	None	None	None	I
R/K	0.1769	likely_benign	0.1564	benign	-0.283	Destabilizing	0.893	D	0.53	neutral	None	None	None	None	I
R/L	0.3447	ambiguous	0.2884	benign	0.536	Stabilizing	0.993	D	0.551	neutral	N	0.495918868	None	None	I
R/M	0.4629	ambiguous	0.411	ambiguous	0.011	Stabilizing	0.999	D	0.655	neutral	None	None	None	None	I
R/N	0.7402	likely_pathogenic	0.6489	pathogenic	0.05	Stabilizing	0.953	D	0.565	neutral	None	None	None	None	I
R/P	0.8943	likely_pathogenic	0.8329	pathogenic	0.301	Stabilizing	0.999	D	0.681	prob.neutral	N	0.488622168	None	None	I
R/Q	0.1393	likely_benign	0.1237	benign	-0.011	Destabilizing	0.997	D	0.597	neutral	N	0.498575171	None	None	I
R/S	0.6269	likely_pathogenic	0.5417	ambiguous	-0.47	Destabilizing	0.953	D	0.566	neutral	None	None	None	None	I
R/T	0.3651	ambiguous	0.3051	benign	-0.173	Destabilizing	0.993	D	0.587	neutral	None	None	None	None	I
R/V	0.4508	ambiguous	0.3776	ambiguous	0.301	Stabilizing	0.993	D	0.693	prob.neutral	None	None	None	None	I
R/W	0.2412	likely_benign	0.2109	benign	0.039	Stabilizing	1.0	D	0.683	prob.neutral	N	0.477519352	None	None	I
R/Y	0.4623	ambiguous	0.387	ambiguous	0.38	Stabilizing	0.986	D	0.683	prob.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.