TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8587	25984;25985;25986	chr2:178715655;178715654;178715653	chr2:179580382;179580381;179580380
N2AB	8270	25033;25034;25035	chr2:178715655;178715654;178715653	chr2:179580382;179580381;179580380
N2A	7343	22252;22253;22254	chr2:178715655;178715654;178715653	chr2:179580382;179580381;179580380
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: GAG
• RefSeq wild type template codon: CTC
• Domain: Ig-71
• Domain position: 39
• Structural Position: 52
• Q(SASA): 0.546
• 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	rs2077371991	None	None	N	0.145	0.068	0.0920862733494	gnomAD-4.0.0	1.59227E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86004E-06	0	0
E/K	rs760340908	-0.022	0.659	N	0.37	0.224	0.20549828249	gnomAD-2.1.1	8.07E-06	None	None	None	None	N	None	0	0	None	0	5.59E-05	None	0	None	0	8.91E-06	0
E/K	rs760340908	-0.022	0.659	N	0.37	0.224	0.20549828249	gnomAD-4.0.0	1.09508E-05	None	None	None	None	N	None	2.98936E-05	0	None	0	2.52181E-05	None	0	0	1.07962E-05	0	3.31422E-05
E/Q	rs760340908	-0.464	0.384	N	0.39	0.173	0.18995819373	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	6.48E-05	0	None	0	0	None	0	None	0	0	0
E/Q	rs760340908	-0.464	0.384	N	0.39	0.173	0.18995819373	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
E/Q	rs760340908	-0.464	0.384	N	0.39	0.173	0.18995819373	gnomAD-4.0.0	6.57609E-06	None	None	None	None	N	None	2.41301E-05	0	None	0	0	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	0.2485	likely_benign	0.2148	benign	-0.358	Destabilizing	0.071	N	0.351	neutral	N	0.511139037	None	None	N
E/C	0.9155	likely_pathogenic	0.892	pathogenic	-0.155	Destabilizing	0.953	D	0.513	neutral	None	None	None	None	N
E/D	0.1084	likely_benign	0.102	benign	-0.269	Destabilizing	None	N	0.145	neutral	N	0.386231101	None	None	N
E/F	0.8373	likely_pathogenic	0.7994	pathogenic	-0.186	Destabilizing	0.908	D	0.455	neutral	None	None	None	None	N
E/G	0.1356	likely_benign	0.1219	benign	-0.536	Destabilizing	0.002	N	0.299	neutral	N	0.408579524	None	None	N
E/H	0.5312	ambiguous	0.4798	ambiguous	0.215	Stabilizing	0.876	D	0.306	neutral	None	None	None	None	N
E/I	0.6174	likely_pathogenic	0.5402	ambiguous	0.075	Stabilizing	0.603	D	0.447	neutral	None	None	None	None	N
E/K	0.1584	likely_benign	0.1349	benign	0.333	Stabilizing	0.659	D	0.37	neutral	N	0.482528284	None	None	N
E/L	0.6272	likely_pathogenic	0.5636	ambiguous	0.075	Stabilizing	0.603	D	0.447	neutral	None	None	None	None	N
E/M	0.5957	likely_pathogenic	0.5321	ambiguous	0.069	Stabilizing	0.757	D	0.422	neutral	None	None	None	None	N
E/N	0.2368	likely_benign	0.2081	benign	-0.04	Destabilizing	0.047	N	0.313	neutral	None	None	None	None	N
E/P	0.8808	likely_pathogenic	0.8492	pathogenic	-0.05	Destabilizing	0.184	N	0.36	neutral	None	None	None	None	N
E/Q	0.1848	likely_benign	0.1696	benign	0.01	Stabilizing	0.384	N	0.39	neutral	N	0.49137984	None	None	N
E/R	0.2817	likely_benign	0.2583	benign	0.592	Stabilizing	0.764	D	0.333	neutral	None	None	None	None	N
E/S	0.2426	likely_benign	0.2129	benign	-0.189	Destabilizing	0.11	N	0.338	neutral	None	None	None	None	N
E/T	0.3448	ambiguous	0.2836	benign	-0.033	Destabilizing	0.254	N	0.368	neutral	None	None	None	None	N
E/V	0.4498	ambiguous	0.3832	ambiguous	-0.05	Destabilizing	0.448	N	0.403	neutral	N	0.465353353	None	None	N
E/W	0.9343	likely_pathogenic	0.9162	pathogenic	-0.022	Destabilizing	0.99	D	0.561	neutral	None	None	None	None	N
E/Y	0.7067	likely_pathogenic	0.658	pathogenic	0.059	Stabilizing	0.963	D	0.415	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.