TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26226	78901;78902;78903	chr2:178567456;178567455;178567454	chr2:179432183;179432182;179432181
N2AB	24585	73978;73979;73980	chr2:178567456;178567455;178567454	chr2:179432183;179432182;179432181
N2A	23658	71197;71198;71199	chr2:178567456;178567455;178567454	chr2:179432183;179432182;179432181
N2B	17161	51706;51707;51708	chr2:178567456;178567455;178567454	chr2:179432183;179432182;179432181
Novex-1	17286	52081;52082;52083	chr2:178567456;178567455;178567454	chr2:179432183;179432182;179432181
Novex-2	17353	52282;52283;52284	chr2:178567456;178567455;178567454	chr2:179432183;179432182;179432181
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: Ig-137
• Domain position: 34
• Structural Position: 47
• Q(SASA): 0.4397
• 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	rs1251054791	-1.164	0.285	N	0.404	0.06	0.211220785272	gnomAD-2.1.1	8.06E-06	None	None	None	None	N	None	0	0	None	0	0	None	6.56E-05	None	0	0	0
E/D	rs1251054791	-1.164	0.285	N	0.404	0.06	0.211220785272	gnomAD-4.0.0	2.05362E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	3.48489E-05	0
E/K	rs754878387	-0.557	0.001	N	0.152	0.255	0.266385636622	gnomAD-2.1.1	5.01E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	4.41023E-04	1.56E-05	1.40924E-04
E/K	rs754878387	-0.557	0.001	N	0.152	0.255	0.266385636622	gnomAD-3.1.2	1.32E-05	None	None	None	None	N	None	0	0	0	0	0	None	9.42E-05	0	1.47E-05	0	0
E/K	rs754878387	-0.557	0.001	N	0.152	0.255	0.266385636622	gnomAD-4.0.0	1.98402E-05	None	None	None	None	N	None	0	0	None	0	0	None	4.06415E-04	0	2.54365E-06	0	4.80554E-05
E/Q	rs754878387	-0.791	0.002	N	0.11	0.096	None	gnomAD-2.1.1	6.8E-05	None	None	None	None	N	None	0	2.83672E-04	None	2.9098E-04	0	None	0	None	0	3.91E-05	1.40924E-04
E/Q	rs754878387	-0.791	0.002	N	0.11	0.096	None	gnomAD-3.1.2	5.26E-05	None	None	None	None	N	None	0	1.96567E-04	0	8.65052E-04	0	None	0	3.16456E-03	1.47E-05	0	0
E/Q	rs754878387	-0.791	0.002	N	0.11	0.096	None	gnomAD-4.0.0	4.15375E-05	None	None	None	None	N	None	0	2.66845E-04	None	3.72024E-04	0	None	0	4.96032E-04	2.54367E-05	0	1.1209E-04

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	0.1367	likely_benign	0.1218	benign	-0.728	Destabilizing	0.001	N	0.239	neutral	N	0.491674282	None	None	N
E/C	0.6701	likely_pathogenic	0.6139	pathogenic	-0.523	Destabilizing	0.972	D	0.541	neutral	None	None	None	None	N
E/D	0.2386	likely_benign	0.1877	benign	-1.191	Destabilizing	0.285	N	0.404	neutral	N	0.494887945	None	None	N
E/F	0.6399	likely_pathogenic	0.5674	pathogenic	-0.004	Destabilizing	0.818	D	0.562	neutral	None	None	None	None	N
E/G	0.2397	likely_benign	0.1968	benign	-1.127	Destabilizing	0.166	N	0.511	neutral	N	0.485620785	None	None	N
E/H	0.3065	likely_benign	0.256	benign	-0.305	Destabilizing	0.901	D	0.476	neutral	None	None	None	None	N
E/I	0.2119	likely_benign	0.1944	benign	0.371	Stabilizing	0.39	N	0.577	neutral	None	None	None	None	N
E/K	0.1154	likely_benign	0.1042	benign	-0.732	Destabilizing	0.001	N	0.152	neutral	N	0.445632561	None	None	N
E/L	0.2757	likely_benign	0.2393	benign	0.371	Stabilizing	0.083	N	0.503	neutral	None	None	None	None	N
E/M	0.3105	likely_benign	0.281	benign	0.737	Stabilizing	0.103	N	0.433	neutral	None	None	None	None	N
E/N	0.2822	likely_benign	0.2284	benign	-1.257	Destabilizing	0.561	D	0.393	neutral	None	None	None	None	N
E/P	0.9758	likely_pathogenic	0.9597	pathogenic	0.027	Stabilizing	0.722	D	0.557	neutral	None	None	None	None	N
E/Q	0.0831	likely_benign	0.0789	benign	-1.076	Destabilizing	0.002	N	0.11	neutral	N	0.397129325	None	None	N
E/R	0.1899	likely_benign	0.1646	benign	-0.415	Destabilizing	0.209	N	0.388	neutral	None	None	None	None	N
E/S	0.1556	likely_benign	0.1322	benign	-1.587	Destabilizing	0.209	N	0.373	neutral	None	None	None	None	N
E/T	0.1251	likely_benign	0.1112	benign	-1.253	Destabilizing	0.345	N	0.495	neutral	None	None	None	None	N
E/V	0.1377	likely_benign	0.1292	benign	0.027	Stabilizing	0.166	N	0.515	neutral	N	0.448558223	None	None	N
E/W	0.8589	likely_pathogenic	0.8004	pathogenic	0.231	Stabilizing	0.991	D	0.553	neutral	None	None	None	None	N
E/Y	0.5469	ambiguous	0.4663	ambiguous	0.241	Stabilizing	0.901	D	0.565	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.