TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5963	18112;18113;18114	chr2:178730646;178730645;178730644	chr2:179595373;179595372;179595371
N2AB	5646	17161;17162;17163	chr2:178730646;178730645;178730644	chr2:179595373;179595372;179595371
N2A	4719	14380;14381;14382	chr2:178730646;178730645;178730644	chr2:179595373;179595372;179595371
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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-43
• Domain position: 45
• Structural Position: 102
• Q(SASA): 0.7197
• 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	rs146983095	-0.216	None	N	0.226	0.11	None	gnomAD-2.1.1	6.24446E-03	None	None	None	None	N	None	1.77774E-03	1.04691E-03	None	1.25871E-03	0	None	2.35356E-03	None	4.91685E-03	1.11904E-02	4.35516E-03
E/G	rs146983095	-0.216	None	N	0.226	0.11	None	gnomAD-3.1.2	6.04128E-03	None	None	None	None	N	None	2.31683E-03	2.55637E-03	5.48246E-03	0	1.93125E-04	None	3.67439E-03	0	1.06442E-02	1.0352E-03	4.77555E-03
E/G	rs146983095	-0.216	None	N	0.226	0.11	None	1000 genomes	2.19649E-03	None	None	None	None	N	None	0	1.4E-03	None	None	0	9.9E-03	None	None	None	0	None
E/G	rs146983095	-0.216	None	N	0.226	0.11	None	gnomAD-4.0.0	9.71013E-03	None	None	None	None	N	None	1.85294E-03	1.7669E-03	None	8.78735E-04	2.22955E-05	None	5.46772E-03	8.25627E-04	1.21964E-02	2.36051E-03	6.94711E-03

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	0.1234	likely_benign	0.1196	benign	-0.088	Destabilizing	0.027	N	0.313	neutral	N	0.39773896	None	None	N
E/C	0.7553	likely_pathogenic	0.7275	pathogenic	-0.081	Destabilizing	0.935	D	0.276	neutral	None	None	None	None	N
E/D	0.066	likely_benign	0.0612	benign	-0.244	Destabilizing	None	N	0.148	neutral	N	0.405779654	None	None	N
E/F	0.6828	likely_pathogenic	0.6783	pathogenic	-0.108	Destabilizing	0.555	D	0.277	neutral	None	None	None	None	N
E/G	0.0949	likely_benign	0.0966	benign	-0.209	Destabilizing	None	N	0.226	neutral	N	0.406875732	None	None	N
E/H	0.3005	likely_benign	0.2825	benign	0.398	Stabilizing	0.001	N	0.196	neutral	None	None	None	None	N
E/I	0.3428	ambiguous	0.336	benign	0.176	Stabilizing	0.555	D	0.299	neutral	None	None	None	None	N
E/K	0.1085	likely_benign	0.1083	benign	0.473	Stabilizing	0.062	N	0.269	neutral	N	0.46840698	None	None	N
E/L	0.326	likely_benign	0.312	benign	0.176	Stabilizing	0.149	N	0.348	neutral	None	None	None	None	N
E/M	0.4289	ambiguous	0.4248	ambiguous	0.06	Stabilizing	0.935	D	0.274	neutral	None	None	None	None	N
E/N	0.131	likely_benign	0.1201	benign	0.205	Stabilizing	0.081	N	0.259	neutral	None	None	None	None	N
E/P	0.2153	likely_benign	0.2014	benign	0.106	Stabilizing	0.555	D	0.315	neutral	None	None	None	None	N
E/Q	0.1131	likely_benign	0.1126	benign	0.225	Stabilizing	0.005	N	0.178	neutral	N	0.465868107	None	None	N
E/R	0.1814	likely_benign	0.1827	benign	0.649	Stabilizing	0.149	N	0.271	neutral	None	None	None	None	N
E/S	0.1139	likely_benign	0.1124	benign	0.076	Stabilizing	0.035	N	0.249	neutral	None	None	None	None	N
E/T	0.1844	likely_benign	0.1762	benign	0.185	Stabilizing	0.149	N	0.37	neutral	None	None	None	None	N
E/V	0.2093	likely_benign	0.2015	benign	0.106	Stabilizing	0.211	N	0.339	neutral	N	0.497268449	None	None	N
E/W	0.783	likely_pathogenic	0.7805	pathogenic	-0.047	Destabilizing	0.935	D	0.299	neutral	None	None	None	None	N
E/Y	0.4939	ambiguous	0.476	ambiguous	0.115	Stabilizing	0.38	N	0.306	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.