TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17712	53359;53360;53361	chr2:178607554;178607553;178607552	chr2:179472281;179472280;179472279
N2AB	16071	48436;48437;48438	chr2:178607554;178607553;178607552	chr2:179472281;179472280;179472279
N2A	15144	45655;45656;45657	chr2:178607554;178607553;178607552	chr2:179472281;179472280;179472279
N2B	8647	26164;26165;26166	chr2:178607554;178607553;178607552	chr2:179472281;179472280;179472279
Novex-1	8772	26539;26540;26541	chr2:178607554;178607553;178607552	chr2:179472281;179472280;179472279
Novex-2	8839	26740;26741;26742	chr2:178607554;178607553;178607552	chr2:179472281;179472280;179472279
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-113
• Domain position: 36
• Structural Position: 56
• Q(SASA): 0.5847
• 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	None	None	0.007	D	0.193	0.241	0.343101102393	gnomAD-4.0.0	1.59239E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86087E-06	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	0.1002	likely_benign	0.097	benign	-0.043	Destabilizing	0.334	N	0.352	neutral	N	0.48530567	None	None	N
E/C	0.5758	likely_pathogenic	0.6247	pathogenic	-0.1	Destabilizing	0.992	D	0.359	neutral	None	None	None	None	N
E/D	0.09	likely_benign	0.077	benign	-0.209	Destabilizing	0.002	N	0.211	neutral	N	0.484438878	None	None	N
E/F	0.4514	ambiguous	0.4791	ambiguous	-0.021	Destabilizing	0.972	D	0.349	neutral	None	None	None	None	N
E/G	0.1223	likely_benign	0.128	benign	-0.177	Destabilizing	0.549	D	0.358	neutral	N	0.500433358	None	None	N
E/H	0.2811	likely_benign	0.2992	benign	0.501	Stabilizing	0.92	D	0.388	neutral	None	None	None	None	N
E/I	0.1495	likely_benign	0.1569	benign	0.256	Stabilizing	0.85	D	0.357	neutral	None	None	None	None	N
E/K	0.1	likely_benign	0.1125	benign	0.497	Stabilizing	0.007	N	0.193	neutral	D	0.53113396	None	None	N
E/L	0.2059	likely_benign	0.221	benign	0.256	Stabilizing	0.617	D	0.355	neutral	None	None	None	None	N
E/M	0.231	likely_benign	0.258	benign	0.082	Stabilizing	0.992	D	0.328	neutral	None	None	None	None	N
E/N	0.139	likely_benign	0.13	benign	0.212	Stabilizing	0.447	N	0.31	neutral	None	None	None	None	N
E/P	0.2694	likely_benign	0.2411	benign	0.175	Stabilizing	0.766	D	0.37	neutral	None	None	None	None	N
E/Q	0.1061	likely_benign	0.1112	benign	0.238	Stabilizing	0.016	N	0.257	neutral	D	0.522034474	None	None	N
E/R	0.1882	likely_benign	0.2108	benign	0.707	Stabilizing	0.447	N	0.307	neutral	None	None	None	None	N
E/S	0.1261	likely_benign	0.1212	benign	0.074	Stabilizing	0.25	N	0.36	neutral	None	None	None	None	N
E/T	0.1221	likely_benign	0.1238	benign	0.193	Stabilizing	0.021	N	0.233	neutral	None	None	None	None	N
E/V	0.1061	likely_benign	0.1058	benign	0.175	Stabilizing	0.549	D	0.367	neutral	N	0.512126912	None	None	N
E/W	0.7288	likely_pathogenic	0.785	pathogenic	0.051	Stabilizing	0.992	D	0.413	neutral	None	None	None	None	N
E/Y	0.3713	ambiguous	0.4072	ambiguous	0.211	Stabilizing	0.972	D	0.348	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.