TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17088	51487;51488;51489	chr2:178610264;178610263;178610262	chr2:179474991;179474990;179474989
N2AB	15447	46564;46565;46566	chr2:178610264;178610263;178610262	chr2:179474991;179474990;179474989
N2A	14520	43783;43784;43785	chr2:178610264;178610263;178610262	chr2:179474991;179474990;179474989
N2B	8023	24292;24293;24294	chr2:178610264;178610263;178610262	chr2:179474991;179474990;179474989
Novex-1	8148	24667;24668;24669	chr2:178610264;178610263;178610262	chr2:179474991;179474990;179474989
Novex-2	8215	24868;24869;24870	chr2:178610264;178610263;178610262	chr2:179474991;179474990;179474989
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: Fn3-12
• Domain position: 42
• Structural Position: 44
• Q(SASA): 0.3194
• 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	None	None	1.0	N	0.715	0.545	0.486422812247	gnomAD-4.0.0	6.84497E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99811E-07	0	0
E/Q	None	None	1.0	N	0.628	0.347	0.478144874143	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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	0.9338	likely_pathogenic	0.9142	pathogenic	-0.741	Destabilizing	0.999	D	0.679	prob.neutral	N	0.479815482	None	None	N
E/C	0.9978	likely_pathogenic	0.9969	pathogenic	-0.453	Destabilizing	1.0	D	0.772	deleterious	None	None	None	None	N
E/D	0.8242	likely_pathogenic	0.8135	pathogenic	-1.117	Destabilizing	0.999	D	0.479	neutral	N	0.497818315	None	None	N
E/F	0.9974	likely_pathogenic	0.9969	pathogenic	0.04	Stabilizing	1.0	D	0.798	deleterious	None	None	None	None	N
E/G	0.9555	likely_pathogenic	0.9442	pathogenic	-1.14	Destabilizing	1.0	D	0.715	prob.delet.	N	0.487412806	None	None	N
E/H	0.9933	likely_pathogenic	0.991	pathogenic	-0.208	Destabilizing	1.0	D	0.666	neutral	None	None	None	None	N
E/I	0.9811	likely_pathogenic	0.9758	pathogenic	0.357	Stabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
E/K	0.9698	likely_pathogenic	0.9607	pathogenic	-0.531	Destabilizing	0.999	D	0.597	neutral	N	0.517249438	None	None	N
E/L	0.9809	likely_pathogenic	0.9769	pathogenic	0.357	Stabilizing	1.0	D	0.819	deleterious	None	None	None	None	N
E/M	0.9824	likely_pathogenic	0.9786	pathogenic	0.736	Stabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	N
E/N	0.983	likely_pathogenic	0.9802	pathogenic	-1.134	Destabilizing	1.0	D	0.723	prob.delet.	None	None	None	None	N
E/P	0.9912	likely_pathogenic	0.9884	pathogenic	0.013	Stabilizing	1.0	D	0.804	deleterious	None	None	None	None	N
E/Q	0.9072	likely_pathogenic	0.8773	pathogenic	-0.961	Destabilizing	1.0	D	0.628	neutral	N	0.481497322	None	None	N
E/R	0.9763	likely_pathogenic	0.9683	pathogenic	-0.205	Destabilizing	1.0	D	0.718	prob.delet.	None	None	None	None	N
E/S	0.9661	likely_pathogenic	0.9592	pathogenic	-1.452	Destabilizing	0.999	D	0.645	neutral	None	None	None	None	N
E/T	0.9756	likely_pathogenic	0.968	pathogenic	-1.111	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
E/V	0.9557	likely_pathogenic	0.9414	pathogenic	0.013	Stabilizing	1.0	D	0.792	deleterious	N	0.487412806	None	None	N
E/W	0.9991	likely_pathogenic	0.9988	pathogenic	0.336	Stabilizing	1.0	D	0.775	deleterious	None	None	None	None	N
E/Y	0.9961	likely_pathogenic	0.995	pathogenic	0.314	Stabilizing	1.0	D	0.787	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.