TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4881	14866;14867;14868	chr2:178735805;178735804;178735803	chr2:179600532;179600531;179600530
N2AB	4564	13915;13916;13917	chr2:178735805;178735804;178735803	chr2:179600532;179600531;179600530
N2A	3637	11134;11135;11136	chr2:178735805;178735804;178735803	chr2:179600532;179600531;179600530
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Ig-31
• Domain position: 87
• Structural Position: 173
• Q(SASA): 0.4602
• 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
E/D	rs781644443	-0.728	0.996	N	0.45	0.332	0.459370960843	gnomAD-2.1.1	1.07E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	2.35E-05	0
E/D	rs781644443	-0.728	0.996	N	0.45	0.332	0.459370960843	gnomAD-3.1.2	2.63E-05	None	None	None	None	I	None	0	0	0	0	0	None	0	0	5.88E-05	0	0
E/D	rs781644443	-0.728	0.996	N	0.45	0.332	0.459370960843	gnomAD-4.0.0	2.29299E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	0	3.13617E-05	0	0
E/G	None	None	0.999	N	0.767	0.657	0.623711697247	gnomAD-4.0.0	1.59152E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85824E-06	0	0
E/Q	rs756371735	-0.297	0.957	N	0.259	0.305	0.363751660372	gnomAD-4.0.0	3.60099E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	3.93753E-06	0	0
E/V	rs2081343515	None	0.999	N	0.817	0.634	0.678242657409	gnomAD-4.0.0	3.18303E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	5.71647E-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
E/A	0.2272	likely_benign	0.1949	benign	-0.969	Destabilizing	0.996	D	0.643	neutral	N	0.517017552	None	None	I
E/C	0.9219	likely_pathogenic	0.8794	pathogenic	-0.426	Destabilizing	1.0	D	0.78	deleterious	None	None	None	None	I
E/D	0.1818	likely_benign	0.1487	benign	-0.974	Destabilizing	0.996	D	0.45	neutral	N	0.506888645	None	None	I
E/F	0.8488	likely_pathogenic	0.7714	pathogenic	-0.256	Destabilizing	1.0	D	0.804	deleterious	None	None	None	None	I
E/G	0.2617	likely_benign	0.2182	benign	-1.349	Destabilizing	0.999	D	0.767	deleterious	N	0.515731111	None	None	I
E/H	0.5114	ambiguous	0.4114	ambiguous	-0.411	Destabilizing	1.0	D	0.679	prob.neutral	None	None	None	None	I
E/I	0.5781	likely_pathogenic	0.4621	ambiguous	0.079	Stabilizing	1.0	D	0.823	deleterious	None	None	None	None	I
E/K	0.1633	likely_benign	0.1348	benign	-0.323	Destabilizing	0.992	D	0.528	neutral	N	0.487130749	None	None	I
E/L	0.5922	likely_pathogenic	0.4849	ambiguous	0.079	Stabilizing	1.0	D	0.795	deleterious	None	None	None	None	I
E/M	0.6273	likely_pathogenic	0.5252	ambiguous	0.521	Stabilizing	1.0	D	0.803	deleterious	None	None	None	None	I
E/N	0.3049	likely_benign	0.2397	benign	-0.949	Destabilizing	1.0	D	0.693	prob.neutral	None	None	None	None	I
E/P	0.7238	likely_pathogenic	0.6681	pathogenic	-0.249	Destabilizing	1.0	D	0.812	deleterious	None	None	None	None	I
E/Q	0.1643	likely_benign	0.1324	benign	-0.813	Destabilizing	0.957	D	0.259	neutral	N	0.455440755	None	None	I
E/R	0.2907	likely_benign	0.2471	benign	-0.045	Destabilizing	0.999	D	0.698	prob.neutral	None	None	None	None	I
E/S	0.2493	likely_benign	0.2053	benign	-1.29	Destabilizing	0.997	D	0.603	neutral	None	None	None	None	I
E/T	0.3016	likely_benign	0.2314	benign	-0.955	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	I
E/V	0.3605	ambiguous	0.2815	benign	-0.249	Destabilizing	0.999	D	0.817	deleterious	N	0.498154653	None	None	I
E/W	0.9354	likely_pathogenic	0.8974	pathogenic	0.106	Stabilizing	1.0	D	0.781	deleterious	None	None	None	None	I
E/Y	0.7226	likely_pathogenic	0.6306	pathogenic	0.061	Stabilizing	1.0	D	0.829	deleterious	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.