TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17925	53998;53999;54000	chr2:178605522;178605521;178605520	chr2:179470249;179470248;179470247
N2AB	16284	49075;49076;49077	chr2:178605522;178605521;178605520	chr2:179470249;179470248;179470247
N2A	15357	46294;46295;46296	chr2:178605522;178605521;178605520	chr2:179470249;179470248;179470247
N2B	8860	26803;26804;26805	chr2:178605522;178605521;178605520	chr2:179470249;179470248;179470247
Novex-1	8985	27178;27179;27180	chr2:178605522;178605521;178605520	chr2:179470249;179470248;179470247
Novex-2	9052	27379;27380;27381	chr2:178605522;178605521;178605520	chr2:179470249;179470248;179470247
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: Fn3-18
• Domain position: 64
• Structural Position: 94
• Q(SASA): 0.6012
• 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/A	rs1488258025	-0.443	0.22	N	0.602	0.239	0.267299060538	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
E/A	rs1488258025	-0.443	0.22	N	0.602	0.239	0.267299060538	gnomAD-4.0.0	6.57903E-06	None	None	None	None	N	None	2.41324E-05	0	None	0	0	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
E/A	0.18	likely_benign	0.1763	benign	-0.48	Destabilizing	0.22	N	0.602	neutral	N	0.502858775	None	None	N
E/C	0.808	likely_pathogenic	0.7813	pathogenic	-0.195	Destabilizing	0.968	D	0.701	prob.neutral	None	None	None	None	N
E/D	0.0921	likely_benign	0.0688	benign	-0.482	Destabilizing	None	N	0.22	neutral	N	0.451507235	None	None	N
E/F	0.8128	likely_pathogenic	0.8189	pathogenic	-0.104	Destabilizing	0.89	D	0.705	prob.neutral	None	None	None	None	N
E/G	0.1538	likely_benign	0.1558	benign	-0.725	Destabilizing	0.22	N	0.598	neutral	N	0.49431665	None	None	N
E/H	0.4317	ambiguous	0.4129	ambiguous	0.136	Stabilizing	0.726	D	0.617	neutral	None	None	None	None	N
E/I	0.5294	ambiguous	0.4979	ambiguous	0.148	Stabilizing	0.726	D	0.721	prob.delet.	None	None	None	None	N
E/K	0.1756	likely_benign	0.1907	benign	0.274	Stabilizing	0.22	N	0.589	neutral	N	0.461953515	None	None	N
E/L	0.4798	ambiguous	0.4872	ambiguous	0.148	Stabilizing	0.726	D	0.684	prob.neutral	None	None	None	None	N
E/M	0.5512	ambiguous	0.5625	ambiguous	0.217	Stabilizing	0.968	D	0.699	prob.neutral	None	None	None	None	N
E/N	0.2065	likely_benign	0.1607	benign	-0.286	Destabilizing	0.157	N	0.571	neutral	None	None	None	None	N
E/P	0.3862	ambiguous	0.3321	benign	-0.04	Destabilizing	0.726	D	0.673	neutral	None	None	None	None	N
E/Q	0.1498	likely_benign	0.1603	benign	-0.206	Destabilizing	0.22	N	0.578	neutral	N	0.484926376	None	None	N
E/R	0.281	likely_benign	0.3062	benign	0.564	Stabilizing	0.567	D	0.615	neutral	None	None	None	None	N
E/S	0.1789	likely_benign	0.1572	benign	-0.428	Destabilizing	0.157	N	0.575	neutral	None	None	None	None	N
E/T	0.1973	likely_benign	0.1825	benign	-0.216	Destabilizing	0.272	N	0.625	neutral	None	None	None	None	N
E/V	0.3036	likely_benign	0.2966	benign	-0.04	Destabilizing	0.667	D	0.653	neutral	N	0.491815062	None	None	N
E/W	0.8837	likely_pathogenic	0.88	pathogenic	0.138	Stabilizing	0.968	D	0.683	prob.neutral	None	None	None	None	N
E/Y	0.6524	likely_pathogenic	0.6262	pathogenic	0.167	Stabilizing	0.89	D	0.705	prob.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.