TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18910	56953;56954;56955	chr2:178598982;178598981;178598980	chr2:179463709;179463708;179463707
N2AB	17269	52030;52031;52032	chr2:178598982;178598981;178598980	chr2:179463709;179463708;179463707
N2A	16342	49249;49250;49251	chr2:178598982;178598981;178598980	chr2:179463709;179463708;179463707
N2B	9845	29758;29759;29760	chr2:178598982;178598981;178598980	chr2:179463709;179463708;179463707
Novex-1	9970	30133;30134;30135	chr2:178598982;178598981;178598980	chr2:179463709;179463708;179463707
Novex-2	10037	30334;30335;30336	chr2:178598982;178598981;178598980	chr2:179463709;179463708;179463707
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Fn3-25
• Domain position: 27
• Structural Position: 29
• Q(SASA): 0.8592
• 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
Y/H	None	None	0.1	N	0.281	0.07	0.173771789658	gnomAD-4.0.0	1.59601E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	2.41896E-04	0	0	0
Y/N	None	None	0.982	N	0.625	0.269	0.365509141856	gnomAD-4.0.0	1.59601E-06	None	None	None	None	I	None	0	0	None	0	2.79298E-05	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
Y/A	0.3886	ambiguous	0.4188	ambiguous	-0.604	Destabilizing	0.953	D	0.503	neutral	None	None	None	None	I
Y/C	0.1834	likely_benign	0.2268	benign	0.142	Stabilizing	0.999	D	0.663	neutral	N	0.472161571	None	None	I
Y/D	0.1225	likely_benign	0.1313	benign	0.977	Stabilizing	0.982	D	0.644	neutral	N	0.408884248	None	None	I
Y/E	0.3979	ambiguous	0.4379	ambiguous	0.955	Stabilizing	0.986	D	0.535	neutral	None	None	None	None	I
Y/F	0.1004	likely_benign	0.0976	benign	-0.29	Destabilizing	0.969	D	0.542	neutral	N	0.476533392	None	None	I
Y/G	0.3738	ambiguous	0.3872	ambiguous	-0.784	Destabilizing	0.986	D	0.574	neutral	None	None	None	None	I
Y/H	0.1529	likely_benign	0.1954	benign	0.247	Stabilizing	0.1	N	0.281	neutral	N	0.48417144	None	None	I
Y/I	0.4877	ambiguous	0.4946	ambiguous	-0.161	Destabilizing	0.993	D	0.626	neutral	None	None	None	None	I
Y/K	0.5145	ambiguous	0.5536	ambiguous	0.241	Stabilizing	0.986	D	0.616	neutral	None	None	None	None	I
Y/L	0.4798	ambiguous	0.4798	ambiguous	-0.161	Destabilizing	0.953	D	0.565	neutral	None	None	None	None	I
Y/M	0.513	ambiguous	0.5079	ambiguous	-0.033	Destabilizing	0.999	D	0.626	neutral	None	None	None	None	I
Y/N	0.0898	likely_benign	0.097	benign	0.054	Stabilizing	0.982	D	0.625	neutral	N	0.466777758	None	None	I
Y/P	0.9368	likely_pathogenic	0.9417	pathogenic	-0.289	Destabilizing	0.998	D	0.661	neutral	None	None	None	None	I
Y/Q	0.4	ambiguous	0.4708	ambiguous	0.101	Stabilizing	0.986	D	0.629	neutral	None	None	None	None	I
Y/R	0.4377	ambiguous	0.4971	ambiguous	0.475	Stabilizing	0.986	D	0.627	neutral	None	None	None	None	I
Y/S	0.1339	likely_benign	0.1483	benign	-0.375	Destabilizing	0.982	D	0.571	neutral	N	0.438148362	None	None	I
Y/T	0.2526	likely_benign	0.2785	benign	-0.308	Destabilizing	0.993	D	0.622	neutral	None	None	None	None	I
Y/V	0.3508	ambiguous	0.3666	ambiguous	-0.289	Destabilizing	0.993	D	0.547	neutral	None	None	None	None	I
Y/W	0.4446	ambiguous	0.4606	ambiguous	-0.433	Destabilizing	0.999	D	0.623	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.