TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21161	63706;63707;63708	chr2:178587926;178587925;178587924	chr2:179452653;179452652;179452651
N2AB	19520	58783;58784;58785	chr2:178587926;178587925;178587924	chr2:179452653;179452652;179452651
N2A	18593	56002;56003;56004	chr2:178587926;178587925;178587924	chr2:179452653;179452652;179452651
N2B	12096	36511;36512;36513	chr2:178587926;178587925;178587924	chr2:179452653;179452652;179452651
Novex-1	12221	36886;36887;36888	chr2:178587926;178587925;178587924	chr2:179452653;179452652;179452651
Novex-2	12288	37087;37088;37089	chr2:178587926;178587925;178587924	chr2:179452653;179452652;179452651
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: Fn3-41
• Domain position: 98
• Structural Position: 125
• Q(SASA): 0.7143
• 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/G	rs765979598	None	0.189	N	0.527	0.109	0.221734844693	gnomAD-4.0.0	1.37998E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.05618E-07	0	1.6714E-05
E/K	rs753274370	0.718	0.189	N	0.609	0.146	None	gnomAD-2.1.1	1.13E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	2.49E-05	0
E/K	rs753274370	0.718	0.189	N	0.609	0.146	None	gnomAD-3.1.2	1.32E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	2.94E-05	0	0
E/K	rs753274370	0.718	0.189	N	0.609	0.146	None	gnomAD-4.0.0	2.99388E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.66393E-05	0	8.05932E-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	0.1167	likely_benign	0.1205	benign	-0.022	Destabilizing	0.189	N	0.619	neutral	N	0.495225435	None	None	N
E/C	0.6763	likely_pathogenic	0.7043	pathogenic	-0.376	Destabilizing	0.962	D	0.785	deleterious	None	None	None	None	N
E/D	0.0694	likely_benign	0.0726	benign	-0.394	Destabilizing	None	N	0.165	neutral	N	0.420055673	None	None	N
E/F	0.6119	likely_pathogenic	0.633	pathogenic	-0.01	Destabilizing	0.962	D	0.761	deleterious	None	None	None	None	N
E/G	0.0987	likely_benign	0.1005	benign	-0.137	Destabilizing	0.189	N	0.527	neutral	N	0.451205299	None	None	N
E/H	0.3698	ambiguous	0.3891	ambiguous	0.683	Stabilizing	0.892	D	0.617	neutral	None	None	None	None	N
E/I	0.3059	likely_benign	0.3227	benign	0.228	Stabilizing	0.687	D	0.801	deleterious	None	None	None	None	N
E/K	0.1779	likely_benign	0.1722	benign	0.329	Stabilizing	0.189	N	0.609	neutral	N	0.48435508	None	None	N
E/L	0.3206	likely_benign	0.3388	benign	0.228	Stabilizing	0.519	D	0.77	deleterious	None	None	None	None	N
E/M	0.3796	ambiguous	0.4062	ambiguous	-0.104	Destabilizing	0.962	D	0.761	deleterious	None	None	None	None	N
E/N	0.1532	likely_benign	0.1582	benign	-0.002	Destabilizing	0.351	N	0.603	neutral	None	None	None	None	N
E/P	0.4771	ambiguous	0.4781	ambiguous	0.162	Stabilizing	0.687	D	0.651	prob.neutral	None	None	None	None	N
E/Q	0.1596	likely_benign	0.1637	benign	0.021	Stabilizing	0.449	N	0.597	neutral	N	0.48677931	None	None	N
E/R	0.2961	likely_benign	0.2937	benign	0.63	Stabilizing	0.519	D	0.65	prob.neutral	None	None	None	None	N
E/S	0.1505	likely_benign	0.1581	benign	-0.12	Destabilizing	0.134	N	0.595	neutral	None	None	None	None	N
E/T	0.1535	likely_benign	0.1642	benign	-0.011	Destabilizing	0.519	D	0.575	neutral	None	None	None	None	N
E/V	0.166	likely_benign	0.1733	benign	0.162	Stabilizing	0.623	D	0.721	deleterious	N	0.498033667	None	None	N
E/W	0.8054	likely_pathogenic	0.8222	pathogenic	0.045	Stabilizing	0.962	D	0.781	deleterious	None	None	None	None	N
E/Y	0.437	ambiguous	0.4598	ambiguous	0.211	Stabilizing	0.962	D	0.749	deleterious	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.