TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30790	92593;92594;92595	chr2:178549258;178549257;178549256	chr2:179413985;179413984;179413983
N2AB	29149	87670;87671;87672	chr2:178549258;178549257;178549256	chr2:179413985;179413984;179413983
N2A	28222	84889;84890;84891	chr2:178549258;178549257;178549256	chr2:179413985;179413984;179413983
N2B	21725	65398;65399;65400	chr2:178549258;178549257;178549256	chr2:179413985;179413984;179413983
Novex-1	21850	65773;65774;65775	chr2:178549258;178549257;178549256	chr2:179413985;179413984;179413983
Novex-2	21917	65974;65975;65976	chr2:178549258;178549257;178549256	chr2:179413985;179413984;179413983
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: Fn3-112
• Domain position: 72
• Structural Position: 103
• Q(SASA): 0.2199
• 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	rs371765494	-1.089	0.999	N	0.596	0.263	None	gnomAD-2.1.1	8.03E-06	None	None	None	None	N	None	0	5.8E-05	None	0	0	None	0	None	0	0	0
E/K	rs371765494	-1.089	0.999	N	0.596	0.263	None	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
E/K	rs371765494	-1.089	0.999	N	0.596	0.263	None	gnomAD-4.0.0	4.33763E-06	None	None	None	None	N	None	1.33479E-05	3.33411E-05	None	0	2.22886E-05	None	0	0	1.69512E-06	0	1.60108E-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	0.3341	likely_benign	0.332	benign	-1.113	Destabilizing	0.999	D	0.673	neutral	N	0.486069679	None	None	N
E/C	0.9109	likely_pathogenic	0.9183	pathogenic	-0.678	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
E/D	0.2265	likely_benign	0.2359	benign	-1.372	Destabilizing	0.999	D	0.467	neutral	N	0.47124388	None	None	N
E/F	0.8531	likely_pathogenic	0.8645	pathogenic	-0.497	Destabilizing	1.0	D	0.824	deleterious	None	None	None	None	N
E/G	0.5087	ambiguous	0.5055	ambiguous	-1.532	Destabilizing	1.0	D	0.735	prob.delet.	N	0.491109335	None	None	N
E/H	0.7697	likely_pathogenic	0.7849	pathogenic	-0.854	Destabilizing	1.0	D	0.699	prob.neutral	None	None	None	None	N
E/I	0.5424	ambiguous	0.5307	ambiguous	0.06	Stabilizing	1.0	D	0.835	deleterious	None	None	None	None	N
E/K	0.574	likely_pathogenic	0.5545	ambiguous	-1.228	Destabilizing	0.999	D	0.596	neutral	N	0.471039616	None	None	N
E/L	0.6524	likely_pathogenic	0.6619	pathogenic	0.06	Stabilizing	1.0	D	0.823	deleterious	None	None	None	None	N
E/M	0.6089	likely_pathogenic	0.6275	pathogenic	0.711	Stabilizing	1.0	D	0.767	deleterious	None	None	None	None	N
E/N	0.5184	ambiguous	0.5391	ambiguous	-1.625	Destabilizing	1.0	D	0.746	deleterious	None	None	None	None	N
E/P	0.9388	likely_pathogenic	0.9279	pathogenic	-0.311	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
E/Q	0.3127	likely_benign	0.3018	benign	-1.424	Destabilizing	1.0	D	0.63	neutral	N	0.469749396	None	None	N
E/R	0.6951	likely_pathogenic	0.6894	pathogenic	-0.947	Destabilizing	1.0	D	0.745	deleterious	None	None	None	None	N
E/S	0.3784	ambiguous	0.3905	ambiguous	-2.099	Highly Destabilizing	0.999	D	0.647	neutral	None	None	None	None	N
E/T	0.3797	ambiguous	0.3866	ambiguous	-1.745	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
E/V	0.3995	ambiguous	0.3865	ambiguous	-0.311	Destabilizing	1.0	D	0.801	deleterious	N	0.470789808	None	None	N
E/W	0.9493	likely_pathogenic	0.9517	pathogenic	-0.317	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
E/Y	0.7718	likely_pathogenic	0.7809	pathogenic	-0.277	Destabilizing	1.0	D	0.811	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.