TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32886	98881;98882;98883	chr2:178539409;178539408;178539407	chr2:179404136;179404135;179404134
N2AB	31245	93958;93959;93960	chr2:178539409;178539408;178539407	chr2:179404136;179404135;179404134
N2A	30318	91177;91178;91179	chr2:178539409;178539408;178539407	chr2:179404136;179404135;179404134
N2B	23821	71686;71687;71688	chr2:178539409;178539408;178539407	chr2:179404136;179404135;179404134
Novex-1	23946	72061;72062;72063	chr2:178539409;178539408;178539407	chr2:179404136;179404135;179404134
Novex-2	24013	72262;72263;72264	chr2:178539409;178539408;178539407	chr2:179404136;179404135;179404134
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: Fn3-127
• Domain position: 92
• Structural Position: 125
• Q(SASA): 0.6927
• 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/A	None	None	0.799	N	0.547	0.119	0.229924730088	gnomAD-4.0.0	6.84682E-07	None	None	None	None	N	None	2.99061E-05	0	None	0	0	None	0	0	0	0	0
E/G	rs1337530273	-0.506	0.012	N	0.525	0.155	0.227934060464	gnomAD-2.1.1	8.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.77E-05	0
E/G	rs1337530273	-0.506	0.012	N	0.525	0.155	0.227934060464	gnomAD-4.0.0	1.36936E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.80036E-06	0	0
E/K	rs767866367	0.425	0.799	N	0.507	0.14	0.221019684889	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
E/K	rs767866367	0.425	0.799	N	0.507	0.14	0.221019684889	gnomAD-4.0.0	1.59413E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43299E-05	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	0.1269	likely_benign	0.143	benign	-0.245	Destabilizing	0.799	D	0.547	neutral	N	0.513909983	None	None	N
E/C	0.7609	likely_pathogenic	0.7751	pathogenic	-0.22	Destabilizing	0.998	D	0.808	deleterious	None	None	None	None	N
E/D	0.1256	likely_benign	0.1231	benign	-0.043	Destabilizing	0.012	N	0.182	neutral	N	0.483413718	None	None	N
E/F	0.5536	ambiguous	0.5957	pathogenic	-0.204	Destabilizing	0.991	D	0.719	prob.delet.	None	None	None	None	N
E/G	0.128	likely_benign	0.1429	benign	-0.396	Destabilizing	0.012	N	0.525	neutral	N	0.460264471	None	None	N
E/H	0.4056	ambiguous	0.4588	ambiguous	0.29	Stabilizing	0.974	D	0.573	neutral	None	None	None	None	N
E/I	0.1883	likely_benign	0.2187	benign	0.109	Stabilizing	0.974	D	0.743	deleterious	None	None	None	None	N
E/K	0.121	likely_benign	0.1529	benign	0.171	Stabilizing	0.799	D	0.507	neutral	N	0.452920637	None	None	N
E/L	0.2823	likely_benign	0.3091	benign	0.109	Stabilizing	0.974	D	0.616	neutral	None	None	None	None	N
E/M	0.3067	likely_benign	0.3389	benign	-0.03	Destabilizing	0.998	D	0.751	deleterious	None	None	None	None	N
E/N	0.1955	likely_benign	0.2152	benign	0.09	Stabilizing	0.066	N	0.323	neutral	None	None	None	None	N
E/P	0.7124	likely_pathogenic	0.7514	pathogenic	0.009	Stabilizing	0.974	D	0.657	prob.neutral	None	None	None	None	N
E/Q	0.1262	likely_benign	0.1456	benign	0.109	Stabilizing	0.966	D	0.586	neutral	N	0.489553043	None	None	N
E/R	0.2249	likely_benign	0.2764	benign	0.469	Stabilizing	0.974	D	0.586	neutral	None	None	None	None	N
E/S	0.173	likely_benign	0.1911	benign	-0.155	Destabilizing	0.841	D	0.504	neutral	None	None	None	None	N
E/T	0.1526	likely_benign	0.1734	benign	-0.034	Destabilizing	0.841	D	0.639	neutral	None	None	None	None	N
E/V	0.1234	likely_benign	0.1418	benign	0.009	Stabilizing	0.966	D	0.627	neutral	N	0.469013884	None	None	N
E/W	0.8413	likely_pathogenic	0.8587	pathogenic	-0.11	Destabilizing	0.998	D	0.819	deleterious	None	None	None	None	N
E/Y	0.4588	ambiguous	0.4858	ambiguous	0.018	Stabilizing	0.991	D	0.762	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.