TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14315	43168;43169;43170	chr2:178633416;178633415;178633414	chr2:179498143;179498142;179498141
N2AB	12674	38245;38246;38247	chr2:178633416;178633415;178633414	chr2:179498143;179498142;179498141
N2A	11747	35464;35465;35466	chr2:178633416;178633415;178633414	chr2:179498143;179498142;179498141
N2B	5250	15973;15974;15975	chr2:178633416;178633415;178633414	chr2:179498143;179498142;179498141
Novex-1	5375	16348;16349;16350	chr2:178633416;178633415;178633414	chr2:179498143;179498142;179498141
Novex-2	5442	16549;16550;16551	chr2:178633416;178633415;178633414	chr2:179498143;179498142;179498141
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-93
• Domain position: 85
• Structural Position: 177
• Q(SASA): 0.7443
• 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
E/Q	None	None	0.942	N	0.475	0.186	0.229924730088	gnomAD-4.0.0	1.59236E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86002E-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	0.2328	likely_benign	0.1796	benign	-0.417	Destabilizing	0.822	D	0.532	neutral	D	0.528611722	None	None	N
E/C	0.9475	likely_pathogenic	0.9289	pathogenic	-0.101	Destabilizing	0.998	D	0.69	prob.neutral	None	None	None	None	N
E/D	0.2367	likely_benign	0.1912	benign	-0.52	Destabilizing	0.014	N	0.317	neutral	N	0.486453421	None	None	N
E/F	0.887	likely_pathogenic	0.8212	pathogenic	-0.217	Destabilizing	0.998	D	0.615	neutral	None	None	None	None	N
E/G	0.2977	likely_benign	0.22	benign	-0.656	Destabilizing	0.822	D	0.478	neutral	D	0.614555023	None	None	N
E/H	0.659	likely_pathogenic	0.6117	pathogenic	-0.105	Destabilizing	0.998	D	0.487	neutral	None	None	None	None	N
E/I	0.5688	likely_pathogenic	0.446	ambiguous	0.189	Stabilizing	0.978	D	0.625	neutral	None	None	None	None	N
E/K	0.2073	likely_benign	0.1706	benign	0.157	Stabilizing	0.058	N	0.381	neutral	N	0.447460011	None	None	N
E/L	0.5944	likely_pathogenic	0.4923	ambiguous	0.189	Stabilizing	0.978	D	0.617	neutral	None	None	None	None	N
E/M	0.6209	likely_pathogenic	0.5332	ambiguous	0.309	Stabilizing	0.998	D	0.577	neutral	None	None	None	None	N
E/N	0.4148	ambiguous	0.3261	benign	-0.189	Destabilizing	0.915	D	0.465	neutral	None	None	None	None	N
E/P	0.9073	likely_pathogenic	0.8727	pathogenic	0.008	Stabilizing	0.978	D	0.508	neutral	None	None	None	None	N
E/Q	0.2015	likely_benign	0.1862	benign	-0.141	Destabilizing	0.942	D	0.475	neutral	N	0.45068069	None	None	N
E/R	0.4022	ambiguous	0.3579	ambiguous	0.393	Stabilizing	0.915	D	0.48	neutral	None	None	None	None	N
E/S	0.3202	likely_benign	0.2495	benign	-0.371	Destabilizing	0.754	D	0.527	neutral	None	None	None	None	N
E/T	0.312	likely_benign	0.2391	benign	-0.181	Destabilizing	0.956	D	0.463	neutral	None	None	None	None	N
E/V	0.3418	ambiguous	0.2627	benign	0.008	Stabilizing	0.971	D	0.558	neutral	D	0.580835791	None	None	N
E/W	0.9666	likely_pathogenic	0.9532	pathogenic	-0.051	Destabilizing	0.998	D	0.706	prob.neutral	None	None	None	None	N
E/Y	0.8269	likely_pathogenic	0.7638	pathogenic	0.029	Stabilizing	0.993	D	0.563	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.