TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14033	42322;42323;42324	chr2:178634777;178634776;178634775	chr2:179499504;179499503;179499502
N2AB	12392	37399;37400;37401	chr2:178634777;178634776;178634775	chr2:179499504;179499503;179499502
N2A	11465	34618;34619;34620	chr2:178634777;178634776;178634775	chr2:179499504;179499503;179499502
N2B	4968	15127;15128;15129	chr2:178634777;178634776;178634775	chr2:179499504;179499503;179499502
Novex-1	5093	15502;15503;15504	chr2:178634777;178634776;178634775	chr2:179499504;179499503;179499502
Novex-2	5160	15703;15704;15705	chr2:178634777;178634776;178634775	chr2:179499504;179499503;179499502
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: Ig-90
• Domain position: 69
• Structural Position: 153
• Q(SASA): 0.412
• 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	rs759297459	-0.909	0.997	N	0.642	0.207	0.223847106136	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	5.58E-05	None	0	None	0	0	0
E/D	rs759297459	-0.909	0.997	N	0.642	0.207	0.223847106136	gnomAD-4.0.0	6.84451E-07	None	None	None	None	N	None	0	0	None	0	2.52169E-05	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	0.8523	likely_pathogenic	0.677	pathogenic	-0.846	Destabilizing	0.997	D	0.779	deleterious	N	0.445979596	None	None	N
E/C	0.9963	likely_pathogenic	0.9925	pathogenic	-0.424	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
E/D	0.7649	likely_pathogenic	0.5262	ambiguous	-0.975	Destabilizing	0.997	D	0.642	neutral	N	0.509903976	None	None	N
E/F	0.9953	likely_pathogenic	0.9864	pathogenic	-0.321	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
E/G	0.9378	likely_pathogenic	0.8492	pathogenic	-1.192	Destabilizing	0.999	D	0.744	deleterious	N	0.429028881	None	None	N
E/H	0.9843	likely_pathogenic	0.9491	pathogenic	-0.535	Destabilizing	1.0	D	0.614	neutral	None	None	None	None	N
E/I	0.9419	likely_pathogenic	0.8609	pathogenic	0.093	Stabilizing	0.999	D	0.803	deleterious	None	None	None	None	N
E/K	0.8802	likely_pathogenic	0.684	pathogenic	-0.46	Destabilizing	0.997	D	0.712	prob.delet.	N	0.465824671	None	None	N
E/L	0.9667	likely_pathogenic	0.9015	pathogenic	0.093	Stabilizing	0.999	D	0.771	deleterious	None	None	None	None	N
E/M	0.9619	likely_pathogenic	0.9002	pathogenic	0.464	Stabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
E/N	0.9387	likely_pathogenic	0.8235	pathogenic	-0.936	Destabilizing	0.999	D	0.682	prob.neutral	None	None	None	None	N
E/P	0.9757	likely_pathogenic	0.926	pathogenic	-0.199	Destabilizing	0.999	D	0.814	deleterious	None	None	None	None	N
E/Q	0.7698	likely_pathogenic	0.5524	ambiguous	-0.821	Destabilizing	0.999	D	0.631	neutral	N	0.447370046	None	None	N
E/R	0.9419	likely_pathogenic	0.8502	pathogenic	-0.19	Destabilizing	0.999	D	0.679	prob.neutral	None	None	None	None	N
E/S	0.9068	likely_pathogenic	0.7648	pathogenic	-1.221	Destabilizing	0.998	D	0.669	prob.neutral	None	None	None	None	N
E/T	0.8847	likely_pathogenic	0.7211	pathogenic	-0.934	Destabilizing	0.999	D	0.829	deleterious	None	None	None	None	N
E/V	0.8755	likely_pathogenic	0.7098	pathogenic	-0.199	Destabilizing	0.999	D	0.767	deleterious	N	0.423570294	None	None	N
E/W	0.9988	likely_pathogenic	0.9969	pathogenic	-0.056	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
E/Y	0.992	likely_pathogenic	0.9762	pathogenic	-0.061	Destabilizing	1.0	D	0.803	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.