TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2335	7228;7229;7230	chr2:178774261;178774260;178774259	chr2:179638988;179638987;179638986
N2AB	2335	7228;7229;7230	chr2:178774261;178774260;178774259	chr2:179638988;179638987;179638986
N2A	2335	7228;7229;7230	chr2:178774261;178774260;178774259	chr2:179638988;179638987;179638986
N2B	2289	7090;7091;7092	chr2:178774261;178774260;178774259	chr2:179638988;179638987;179638986
Novex-1	2289	7090;7091;7092	chr2:178774261;178774260;178774259	chr2:179638988;179638987;179638986
Novex-2	2289	7090;7091;7092	chr2:178774261;178774260;178774259	chr2:179638988;179638987;179638986
Novex-3	2335	7228;7229;7230	chr2:178774261;178774260;178774259	chr2:179638988;179638987;179638986

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-12
• Domain position: 69
• Structural Position: 153
• Q(SASA): 0.4032
• 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	rs756497839	-0.625	0.014	N	0.193	0.258	0.238705975628	gnomAD-2.1.1	1.06E-05	None	None	None	None	N	None	0	0	None	0	1.50602E-04	None	0	None	0	0	0
E/K	rs756497839	-0.625	0.014	N	0.193	0.258	0.238705975628	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	0	0	0	0	3.84468E-04	None	0	0	0	0	0
E/K	rs756497839	-0.625	0.014	N	0.193	0.258	0.238705975628	gnomAD-4.0.0	4.95636E-06	None	None	None	None	N	None	0	0	None	0	1.78269E-04	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	0.1133	likely_benign	0.1096	benign	-0.458	Destabilizing	0.565	D	0.607	neutral	N	0.501573347	None	None	N
E/C	0.6719	likely_pathogenic	0.6537	pathogenic	-0.223	Destabilizing	0.996	D	0.716	prob.delet.	None	None	None	None	N
E/D	0.1179	likely_benign	0.116	benign	-1.17	Destabilizing	0.722	D	0.543	neutral	N	0.40362138	None	None	N
E/F	0.4901	ambiguous	0.474	ambiguous	-0.639	Destabilizing	0.987	D	0.72	prob.delet.	None	None	None	None	N
E/G	0.1619	likely_benign	0.1613	benign	-0.767	Destabilizing	0.722	D	0.655	neutral	N	0.504336304	None	None	N
E/H	0.2993	likely_benign	0.2952	benign	-1.077	Destabilizing	0.923	D	0.615	neutral	None	None	None	None	N
E/I	0.1453	likely_benign	0.1343	benign	0.356	Stabilizing	0.961	D	0.725	prob.delet.	None	None	None	None	N
E/K	0.0983	likely_benign	0.0972	benign	-0.501	Destabilizing	0.014	N	0.193	neutral	N	0.4833356	None	None	N
E/L	0.1957	likely_benign	0.187	benign	0.356	Stabilizing	0.775	D	0.66	neutral	None	None	None	None	N
E/M	0.2342	likely_benign	0.2244	benign	0.846	Stabilizing	0.989	D	0.705	prob.neutral	None	None	None	None	N
E/N	0.1374	likely_benign	0.13	benign	-0.746	Destabilizing	0.775	D	0.569	neutral	None	None	None	None	N
E/P	0.4244	ambiguous	0.4204	ambiguous	0.107	Stabilizing	0.961	D	0.665	neutral	None	None	None	None	N
E/Q	0.0943	likely_benign	0.0933	benign	-0.649	Destabilizing	0.034	N	0.253	neutral	N	0.504426772	None	None	N
E/R	0.177	likely_benign	0.1799	benign	-0.518	Destabilizing	0.633	D	0.553	neutral	None	None	None	None	N
E/S	0.1369	likely_benign	0.1336	benign	-1.039	Destabilizing	0.633	D	0.566	neutral	None	None	None	None	N
E/T	0.115	likely_benign	0.1096	benign	-0.787	Destabilizing	0.775	D	0.618	neutral	None	None	None	None	N
E/V	0.1057	likely_benign	0.1006	benign	0.107	Stabilizing	0.901	D	0.659	neutral	N	0.486027254	None	None	N
E/W	0.7594	likely_pathogenic	0.7472	pathogenic	-0.711	Destabilizing	0.996	D	0.702	prob.neutral	None	None	None	None	N
E/Y	0.4166	ambiguous	0.408	ambiguous	-0.46	Destabilizing	0.961	D	0.72	prob.delet.	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.