TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4025	12298;12299;12300	chr2:178741160;178741159;178741158	chr2:179605887;179605886;179605885
N2AB	3708	11347;11348;11349	chr2:178741160;178741159;178741158	chr2:179605887;179605886;179605885
N2A	None	None	chr2:None	chr2:None
N2B	3662	11209;11210;11211	chr2:178741160;178741159;178741158	chr2:179605887;179605886;179605885
Novex-1	3787	11584;11585;11586	chr2:178741160;178741159;178741158	chr2:179605887;179605886;179605885
Novex-2	3854	11785;11786;11787	chr2:178741160;178741159;178741158	chr2:179605887;179605886;179605885
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-28
• Domain position: 88
• Structural Position: 173
• Q(SASA): 0.4909
• 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/G	rs1452131866	None	0.505	D	0.705	0.487	None	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
E/G	rs1452131866	None	0.505	D	0.705	0.487	None	gnomAD-4.0.0	2.56281E-06	None	None	None	None	N	None	1.6905E-05	0	None	0	0	None	0	0	2.39277E-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	0.2417	likely_benign	0.2666	benign	-0.679	Destabilizing	0.338	N	0.675	prob.neutral	D	0.539195522	None	None	N
E/C	0.9184	likely_pathogenic	0.9209	pathogenic	-0.343	Destabilizing	0.991	D	0.723	prob.delet.	None	None	None	None	N
E/D	0.2672	likely_benign	0.2949	benign	-0.792	Destabilizing	0.003	N	0.298	neutral	D	0.547604308	None	None	N
E/F	0.841	likely_pathogenic	0.8563	pathogenic	0.049	Stabilizing	0.967	D	0.749	deleterious	None	None	None	None	N
E/G	0.2887	likely_benign	0.3049	benign	-1.039	Destabilizing	0.505	D	0.705	prob.neutral	D	0.672571961	None	None	N
E/H	0.5145	ambiguous	0.5533	ambiguous	-0.056	Destabilizing	0.826	D	0.645	neutral	None	None	None	None	N
E/I	0.5785	likely_pathogenic	0.5987	pathogenic	0.298	Stabilizing	0.906	D	0.759	deleterious	None	None	None	None	N
E/K	0.1341	likely_benign	0.1356	benign	-0.152	Destabilizing	0.013	N	0.365	neutral	N	0.503933732	None	None	N
E/L	0.5854	likely_pathogenic	0.6034	pathogenic	0.298	Stabilizing	0.826	D	0.711	prob.delet.	None	None	None	None	N
E/M	0.6297	likely_pathogenic	0.6497	pathogenic	0.565	Stabilizing	0.973	D	0.743	deleterious	None	None	None	None	N
E/N	0.3784	ambiguous	0.4127	ambiguous	-0.82	Destabilizing	0.404	N	0.632	neutral	None	None	None	None	N
E/P	0.6939	likely_pathogenic	0.742	pathogenic	-0.006	Destabilizing	0.906	D	0.751	deleterious	None	None	None	None	N
E/Q	0.151	likely_benign	0.1561	benign	-0.667	Destabilizing	0.007	N	0.291	neutral	N	0.515970534	None	None	N
E/R	0.25	likely_benign	0.2539	benign	0.15	Stabilizing	0.404	N	0.632	neutral	None	None	None	None	N
E/S	0.278	likely_benign	0.302	benign	-1.071	Destabilizing	0.404	N	0.618	neutral	None	None	None	None	N
E/T	0.3245	likely_benign	0.3496	ambiguous	-0.758	Destabilizing	0.826	D	0.72	prob.delet.	None	None	None	None	N
E/V	0.3653	ambiguous	0.3771	ambiguous	-0.006	Destabilizing	0.782	D	0.708	prob.delet.	N	0.507884418	None	None	N
E/W	0.9335	likely_pathogenic	0.939	pathogenic	0.375	Stabilizing	0.991	D	0.698	prob.neutral	None	None	None	None	N
E/Y	0.708	likely_pathogenic	0.7368	pathogenic	0.34	Stabilizing	0.906	D	0.761	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.