TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25209	75850;75851;75852	chr2:178570507;178570506;178570505	chr2:179435234;179435233;179435232
N2AB	23568	70927;70928;70929	chr2:178570507;178570506;178570505	chr2:179435234;179435233;179435232
N2A	22641	68146;68147;68148	chr2:178570507;178570506;178570505	chr2:179435234;179435233;179435232
N2B	16144	48655;48656;48657	chr2:178570507;178570506;178570505	chr2:179435234;179435233;179435232
Novex-1	16269	49030;49031;49032	chr2:178570507;178570506;178570505	chr2:179435234;179435233;179435232
Novex-2	16336	49231;49232;49233	chr2:178570507;178570506;178570505	chr2:179435234;179435233;179435232
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: Fn3-71
• Domain position: 6
• Structural Position: 6
• Q(SASA): 0.2997
• 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/K	rs773767237	-0.765	0.008	N	0.405	0.127	0.176091768786	gnomAD-2.1.1	1.21E-05	None	None	None	None	N	None	0	5.81E-05	None	9.97E-05	0	None	0	None	0	0	0
E/K	rs773767237	-0.765	0.008	N	0.405	0.127	0.176091768786	gnomAD-3.1.2	1.32E-05	None	None	None	None	N	None	0	6.56E-05	0	0	0	None	0	0	0	0	4.78927E-04
E/K	rs773767237	-0.765	0.008	N	0.405	0.127	0.176091768786	gnomAD-4.0.0	1.15378E-05	None	None	None	None	N	None	0	1.01778E-04	None	0	0	None	0	0	0	0	8.53922E-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	0.1171	likely_benign	0.1214	benign	-0.638	Destabilizing	0.565	D	0.519	neutral	N	0.456304474	None	None	N
E/C	0.7399	likely_pathogenic	0.7691	pathogenic	-0.464	Destabilizing	0.996	D	0.799	deleterious	None	None	None	None	N
E/D	0.2465	likely_benign	0.2636	benign	-0.858	Destabilizing	0.003	N	0.211	neutral	N	0.452496165	None	None	N
E/F	0.7599	likely_pathogenic	0.7796	pathogenic	-0.011	Destabilizing	0.987	D	0.784	deleterious	None	None	None	None	N
E/G	0.1909	likely_benign	0.1928	benign	-0.974	Destabilizing	0.722	D	0.625	neutral	N	0.474332875	None	None	N
E/H	0.5451	ambiguous	0.5754	pathogenic	-0.096	Destabilizing	0.989	D	0.547	neutral	None	None	None	None	N
E/I	0.2902	likely_benign	0.3115	benign	0.267	Stabilizing	0.961	D	0.767	deleterious	None	None	None	None	N
E/K	0.1851	likely_benign	0.1982	benign	-0.454	Destabilizing	0.008	N	0.405	neutral	N	0.489358255	None	None	N
E/L	0.3636	ambiguous	0.3941	ambiguous	0.267	Stabilizing	0.923	D	0.735	prob.delet.	None	None	None	None	N
E/M	0.3758	ambiguous	0.4104	ambiguous	0.45	Stabilizing	0.996	D	0.763	deleterious	None	None	None	None	N
E/N	0.3884	ambiguous	0.4136	ambiguous	-0.952	Destabilizing	0.775	D	0.545	neutral	None	None	None	None	N
E/P	0.8729	likely_pathogenic	0.8922	pathogenic	-0.013	Destabilizing	0.961	D	0.601	neutral	None	None	None	None	N
E/Q	0.1304	likely_benign	0.1351	benign	-0.809	Destabilizing	0.565	D	0.55	neutral	N	0.45495768	None	None	N
E/R	0.2931	likely_benign	0.3118	benign	-0.085	Destabilizing	0.858	D	0.541	neutral	None	None	None	None	N
E/S	0.1926	likely_benign	0.2106	benign	-1.191	Destabilizing	0.633	D	0.505	neutral	None	None	None	None	N
E/T	0.2024	likely_benign	0.2189	benign	-0.914	Destabilizing	0.923	D	0.593	neutral	None	None	None	None	N
E/V	0.1506	likely_benign	0.1598	benign	-0.013	Destabilizing	0.901	D	0.683	prob.neutral	N	0.478602544	None	None	N
E/W	0.9276	likely_pathogenic	0.9395	pathogenic	0.24	Stabilizing	0.996	D	0.788	deleterious	None	None	None	None	N
E/Y	0.665	likely_pathogenic	0.6935	pathogenic	0.229	Stabilizing	0.987	D	0.743	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.