TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25978	78157;78158;78159	chr2:178568200;178568199;178568198	chr2:179432927;179432926;179432925
N2AB	24337	73234;73235;73236	chr2:178568200;178568199;178568198	chr2:179432927;179432926;179432925
N2A	23410	70453;70454;70455	chr2:178568200;178568199;178568198	chr2:179432927;179432926;179432925
N2B	16913	50962;50963;50964	chr2:178568200;178568199;178568198	chr2:179432927;179432926;179432925
Novex-1	17038	51337;51338;51339	chr2:178568200;178568199;178568198	chr2:179432927;179432926;179432925
Novex-2	17105	51538;51539;51540	chr2:178568200;178568199;178568198	chr2:179432927;179432926;179432925
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: Fn3-76
• Domain position: 89
• Structural Position: 122
• Q(SASA): 0.8256
• 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/D	rs1025712241	None	None	N	0.109	0.084	0.0954503805726	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
E/D	rs1025712241	None	None	N	0.109	0.084	0.0954503805726	gnomAD-4.0.0	6.57886E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.47106E-05	0	0
E/G	None	None	0.361	N	0.508	0.175	0.326881540566	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
E/Q	rs767541275	0.451	0.361	N	0.541	0.186	0.285698343383	gnomAD-2.1.1	8.04E-06	None	None	None	None	N	None	0	0	None	0	1.11346E-04	None	0	None	0	0	0
E/Q	rs767541275	0.451	0.361	N	0.541	0.186	0.285698343383	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
E/Q	rs767541275	0.451	0.361	N	0.541	0.186	0.285698343383	gnomAD-4.0.0	7.68984E-06	None	None	None	None	N	None	0	0	None	0	4.85178E-05	None	0	0	7.18267E-06	1.34034E-05	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	0.1607	likely_benign	0.1825	benign	-0.902	Destabilizing	0.104	N	0.422	neutral	N	0.482094704	None	None	N
E/C	0.7591	likely_pathogenic	0.7757	pathogenic	-0.443	Destabilizing	0.984	D	0.524	neutral	None	None	None	None	N
E/D	0.0921	likely_benign	0.0889	benign	-0.973	Destabilizing	None	N	0.109	neutral	N	0.477067401	None	None	N
E/F	0.6449	likely_pathogenic	0.6788	pathogenic	-0.133	Destabilizing	0.724	D	0.51	neutral	None	None	None	None	N
E/G	0.2575	likely_benign	0.2855	benign	-1.285	Destabilizing	0.361	N	0.508	neutral	N	0.500389997	None	None	N
E/H	0.4931	ambiguous	0.5418	ambiguous	-0.244	Destabilizing	0.942	D	0.465	neutral	None	None	None	None	N
E/I	0.2143	likely_benign	0.2289	benign	0.153	Stabilizing	0.272	N	0.54	neutral	None	None	None	None	N
E/K	0.2884	likely_benign	0.3365	benign	-0.414	Destabilizing	0.361	N	0.417	neutral	D	0.524935919	None	None	N
E/L	0.274	likely_benign	0.309	benign	0.153	Stabilizing	0.272	N	0.543	neutral	None	None	None	None	N
E/M	0.3747	ambiguous	0.4042	ambiguous	0.551	Stabilizing	0.953	D	0.514	neutral	None	None	None	None	N
E/N	0.1992	likely_benign	0.2199	benign	-1.048	Destabilizing	0.272	N	0.465	neutral	None	None	None	None	N
E/P	0.4448	ambiguous	0.524	ambiguous	-0.178	Destabilizing	0.842	D	0.508	neutral	None	None	None	None	N
E/Q	0.1816	likely_benign	0.2035	benign	-0.896	Destabilizing	0.361	N	0.541	neutral	N	0.508427672	None	None	N
E/R	0.4368	ambiguous	0.4952	ambiguous	-0.062	Destabilizing	0.842	D	0.508	neutral	None	None	None	None	N
E/S	0.1936	likely_benign	0.2087	benign	-1.366	Destabilizing	0.272	N	0.381	neutral	None	None	None	None	N
E/T	0.1623	likely_benign	0.1751	benign	-1.035	Destabilizing	0.428	N	0.423	neutral	None	None	None	None	N
E/V	0.1277	likely_benign	0.1375	benign	-0.178	Destabilizing	0.001	N	0.315	neutral	N	0.513585562	None	None	N
E/W	0.8949	likely_pathogenic	0.9076	pathogenic	0.221	Stabilizing	0.984	D	0.61	neutral	None	None	None	None	N
E/Y	0.5559	ambiguous	0.596	pathogenic	0.168	Stabilizing	0.842	D	0.529	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.