TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32764	98515;98516;98517	chr2:178539775;178539774;178539773	chr2:179404502;179404501;179404500
N2AB	31123	93592;93593;93594	chr2:178539775;178539774;178539773	chr2:179404502;179404501;179404500
N2A	30196	90811;90812;90813	chr2:178539775;178539774;178539773	chr2:179404502;179404501;179404500
N2B	23699	71320;71321;71322	chr2:178539775;178539774;178539773	chr2:179404502;179404501;179404500
Novex-1	23824	71695;71696;71697	chr2:178539775;178539774;178539773	chr2:179404502;179404501;179404500
Novex-2	23891	71896;71897;71898	chr2:178539775;178539774;178539773	chr2:179404502;179404501;179404500
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: Ig-155
• Domain position: 57
• Structural Position: 143
• Q(SASA): 0.6088
• 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	-0.226	0.939	N	0.551	0.242	0.239305524855	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.88E-06	0
E/A	None	-0.226	0.939	N	0.551	0.242	0.239305524855	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
E/A	None	-0.226	0.939	N	0.551	0.242	0.239305524855	gnomAD-4.0.0	5.12407E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.57213E-06	0	0
E/G	rs755276825	-0.563	0.939	N	0.545	0.292	0.251116650651	gnomAD-2.1.1	8.04E-06	None	None	None	None	N	None	0	0	None	0	1.11421E-04	None	0	None	0	0	0
E/G	rs755276825	-0.563	0.939	N	0.545	0.292	0.251116650651	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	1.92827E-04	None	0	0	0	0	0
E/G	rs755276825	-0.563	0.939	N	0.545	0.292	0.251116650651	gnomAD-4.0.0	3.84305E-06	None	None	None	None	N	None	0	0	None	0	7.27273E-05	None	0	0	0	0	0
E/K	rs781604869	0.663	0.939	N	0.505	0.258	0.190952846119	gnomAD-2.1.1	8.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.78E-05	0
E/K	rs781604869	0.663	0.939	N	0.505	0.258	0.190952846119	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
E/K	rs781604869	0.663	0.939	N	0.505	0.258	0.190952846119	gnomAD-4.0.0	7.6862E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.43578E-05	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	0.166	likely_benign	0.1756	benign	-0.167	Destabilizing	0.939	D	0.551	neutral	N	0.459075421	None	None	N
E/C	0.8381	likely_pathogenic	0.8588	pathogenic	0.08	Stabilizing	0.999	D	0.75	deleterious	None	None	None	None	N
E/D	0.088	likely_benign	0.0918	benign	-0.171	Destabilizing	0.02	N	0.248	neutral	N	0.388673973	None	None	N
E/F	0.78	likely_pathogenic	0.7834	pathogenic	-0.172	Destabilizing	0.999	D	0.731	prob.delet.	None	None	None	None	N
E/G	0.1294	likely_benign	0.1333	benign	-0.328	Destabilizing	0.939	D	0.545	neutral	N	0.430811384	None	None	N
E/H	0.525	ambiguous	0.5414	ambiguous	0.139	Stabilizing	0.999	D	0.586	neutral	None	None	None	None	N
E/I	0.5656	likely_pathogenic	0.5828	pathogenic	0.21	Stabilizing	0.993	D	0.754	deleterious	None	None	None	None	N
E/K	0.2604	likely_benign	0.261	benign	0.488	Stabilizing	0.939	D	0.505	neutral	N	0.429232516	None	None	N
E/L	0.5266	ambiguous	0.5431	ambiguous	0.21	Stabilizing	0.993	D	0.734	prob.delet.	None	None	None	None	N
E/M	0.5431	ambiguous	0.5489	ambiguous	0.23	Stabilizing	0.999	D	0.685	prob.neutral	None	None	None	None	N
E/N	0.175	likely_benign	0.1761	benign	0.267	Stabilizing	0.973	D	0.566	neutral	None	None	None	None	N
E/P	0.8423	likely_pathogenic	0.8509	pathogenic	0.104	Stabilizing	0.993	D	0.651	neutral	None	None	None	None	N
E/Q	0.1844	likely_benign	0.188	benign	0.29	Stabilizing	0.991	D	0.573	neutral	N	0.457363267	None	None	N
E/R	0.3934	ambiguous	0.3933	ambiguous	0.637	Stabilizing	0.993	D	0.615	neutral	None	None	None	None	N
E/S	0.2037	likely_benign	0.2077	benign	0.1	Stabilizing	0.953	D	0.508	neutral	None	None	None	None	N
E/T	0.267	likely_benign	0.2778	benign	0.233	Stabilizing	0.986	D	0.59	neutral	None	None	None	None	N
E/V	0.3345	likely_benign	0.3512	ambiguous	0.104	Stabilizing	0.991	D	0.696	prob.neutral	N	0.482568356	None	None	N
E/W	0.9045	likely_pathogenic	0.9152	pathogenic	-0.088	Destabilizing	0.999	D	0.751	deleterious	None	None	None	None	N
E/Y	0.5917	likely_pathogenic	0.6057	pathogenic	0.062	Stabilizing	0.999	D	0.694	prob.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.