TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7651	23176;23177;23178	chr2:178721068;178721067;178721066	chr2:179585795;179585794;179585793
N2AB	7334	22225;22226;22227	chr2:178721068;178721067;178721066	chr2:179585795;179585794;179585793
N2A	6407	19444;19445;19446	chr2:178721068;178721067;178721066	chr2:179585795;179585794;179585793
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-61
• Domain position: 44
• Structural Position: 70
• Q(SASA): 0.3716
• 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	rs1461872954	-0.791	0.248	N	0.241	0.22	0.402614778071	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	6.47E-05	0	None	0	0	None	0	None	0	0	0
E/G	rs1461872954	-0.791	0.248	N	0.241	0.22	0.402614778071	gnomAD-3.1.2	2.63E-05	None	None	None	None	N	None	9.65E-05	0	0	0	0	None	0	0	0	0	0
E/G	rs1461872954	-0.791	0.248	N	0.241	0.22	0.402614778071	gnomAD-4.0.0	5.57904E-06	None	None	None	None	N	None	1.06803E-04	0	None	0	0	None	0	0	8.47909E-07	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	0.1005	likely_benign	0.1101	benign	-0.323	Destabilizing	None	N	0.125	neutral	N	0.434396847	None	None	N
E/C	0.7826	likely_pathogenic	0.8355	pathogenic	0.106	Stabilizing	0.945	D	0.303	neutral	None	None	None	None	N
E/D	0.1169	likely_benign	0.1173	benign	-0.276	Destabilizing	0.049	N	0.18	neutral	N	0.428895026	None	None	N
E/F	0.6945	likely_pathogenic	0.7805	pathogenic	-0.341	Destabilizing	0.893	D	0.359	neutral	None	None	None	None	N
E/G	0.1103	likely_benign	0.1272	benign	-0.504	Destabilizing	0.248	N	0.241	neutral	N	0.46254624	None	None	N
E/H	0.3175	likely_benign	0.3842	ambiguous	-0.178	Destabilizing	0.003	N	0.147	neutral	None	None	None	None	N
E/I	0.3604	ambiguous	0.4338	ambiguous	0.112	Stabilizing	0.355	N	0.377	neutral	None	None	None	None	N
E/K	0.09	likely_benign	0.1111	benign	0.365	Stabilizing	0.268	N	0.155	neutral	N	0.494463871	None	None	N
E/L	0.3607	ambiguous	0.4333	ambiguous	0.112	Stabilizing	0.185	N	0.317	neutral	None	None	None	None	N
E/M	0.4322	ambiguous	0.4936	ambiguous	0.271	Stabilizing	0.681	D	0.309	neutral	None	None	None	None	N
E/N	0.1986	likely_benign	0.2207	benign	0.155	Stabilizing	0.204	N	0.14	neutral	None	None	None	None	N
E/P	0.2086	likely_benign	0.2559	benign	-0.013	Destabilizing	None	N	0.129	neutral	None	None	None	None	N
E/Q	0.0991	likely_benign	0.1088	benign	0.178	Stabilizing	0.563	D	0.177	neutral	N	0.483689516	None	None	N
E/R	0.1519	likely_benign	0.1934	benign	0.486	Stabilizing	0.54	D	0.143	neutral	None	None	None	None	N
E/S	0.1361	likely_benign	0.1525	benign	-0.013	Destabilizing	0.116	N	0.172	neutral	None	None	None	None	N
E/T	0.176	likely_benign	0.2042	benign	0.132	Stabilizing	0.266	N	0.263	neutral	None	None	None	None	N
E/V	0.2071	likely_benign	0.2471	benign	-0.013	Destabilizing	0.057	N	0.265	neutral	N	0.489039408	None	None	N
E/W	0.8322	likely_pathogenic	0.8998	pathogenic	-0.243	Destabilizing	0.996	D	0.317	neutral	None	None	None	None	N
E/Y	0.4884	ambiguous	0.6003	pathogenic	-0.11	Destabilizing	0.917	D	0.395	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.