TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5609	17050;17051;17052	chr2:178732144;178732143;178732142	chr2:179596871;179596870;179596869
N2AB	5292	16099;16100;16101	chr2:178732144;178732143;178732142	chr2:179596871;179596870;179596869
N2A	4365	13318;13319;13320	chr2:178732144;178732143;178732142	chr2:179596871;179596870;179596869
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: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-39
• Domain position: 67
• Structural Position: 148
• Q(SASA): 0.5174
• 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/G	None	None	0.822	N	0.473	0.25	0.327419511103	gnomAD-4.0.0	1.59132E-06	None	None	None	None	I	None	0	0	None	4.76781E-05	0	None	0	0	0	0	0
E/K	rs374682077	0.85	0.963	N	0.48	0.29	None	gnomAD-2.1.1	3.22E-05	None	None	None	None	I	None	1.65399E-04	2.83E-05	None	0	0	None	3.27E-05	None	0	1.56E-05	1.40647E-04
E/K	rs374682077	0.85	0.963	N	0.48	0.29	None	gnomAD-3.1.2	7.89E-05	None	None	None	None	I	None	2.41301E-04	0	0	0	0	None	0	0	1.47E-05	0	4.78927E-04
E/K	rs374682077	0.85	0.963	N	0.48	0.29	None	gnomAD-4.0.0	2.04492E-05	None	None	None	None	I	None	1.73264E-04	1.66639E-05	None	0	4.45752E-05	None	3.12461E-05	0	1.10193E-05	1.0982E-05	1.60067E-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
E/A	0.1163	likely_benign	0.1334	benign	-0.378	Destabilizing	0.058	N	0.323	neutral	N	0.511525826	None	None	I
E/C	0.7109	likely_pathogenic	0.7586	pathogenic	-0.043	Destabilizing	0.998	D	0.652	neutral	None	None	None	None	I
E/D	0.0938	likely_benign	0.1012	benign	-0.252	Destabilizing	0.014	N	0.297	neutral	N	0.500058039	None	None	I
E/F	0.582	likely_pathogenic	0.643	pathogenic	-0.298	Destabilizing	0.993	D	0.633	neutral	None	None	None	None	I
E/G	0.1027	likely_benign	0.1124	benign	-0.542	Destabilizing	0.822	D	0.473	neutral	N	0.47552157	None	None	I
E/H	0.2955	likely_benign	0.3389	benign	0.058	Stabilizing	0.998	D	0.46	neutral	None	None	None	None	I
E/I	0.2864	likely_benign	0.3378	benign	0.012	Stabilizing	0.978	D	0.631	neutral	None	None	None	None	I
E/K	0.0982	likely_benign	0.1105	benign	0.387	Stabilizing	0.963	D	0.48	neutral	N	0.464165265	None	None	I
E/L	0.2859	likely_benign	0.3418	ambiguous	0.012	Stabilizing	0.956	D	0.551	neutral	None	None	None	None	I
E/M	0.3404	ambiguous	0.3964	ambiguous	0.104	Stabilizing	0.998	D	0.565	neutral	None	None	None	None	I
E/N	0.1707	likely_benign	0.19	benign	0.047	Stabilizing	0.915	D	0.461	neutral	None	None	None	None	I
E/P	0.4301	ambiguous	0.5049	ambiguous	-0.1	Destabilizing	0.978	D	0.493	neutral	None	None	None	None	I
E/Q	0.1109	likely_benign	0.1262	benign	0.084	Stabilizing	0.976	D	0.466	neutral	N	0.473724371	None	None	I
E/R	0.1577	likely_benign	0.176	benign	0.577	Stabilizing	0.978	D	0.475	neutral	None	None	None	None	I
E/S	0.1341	likely_benign	0.1481	benign	-0.096	Destabilizing	0.754	D	0.456	neutral	None	None	None	None	I
E/T	0.1527	likely_benign	0.1777	benign	0.047	Stabilizing	0.86	D	0.453	neutral	None	None	None	None	I
E/V	0.178	likely_benign	0.21	benign	-0.1	Destabilizing	0.942	D	0.451	neutral	N	0.503794043	None	None	I
E/W	0.6943	likely_pathogenic	0.7444	pathogenic	-0.159	Destabilizing	0.998	D	0.691	prob.neutral	None	None	None	None	I
E/Y	0.4515	ambiguous	0.5048	ambiguous	-0.062	Destabilizing	0.993	D	0.576	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.