TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8300	25123;25124;25125	chr2:178718108;178718107;178718106	chr2:179582835;179582834;179582833
N2AB	7983	24172;24173;24174	chr2:178718108;178718107;178718106	chr2:179582835;179582834;179582833
N2A	7056	21391;21392;21393	chr2:178718108;178718107;178718106	chr2:179582835;179582834;179582833
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: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-68
• Domain position: 37
• Structural Position: 51
• Q(SASA): 0.6243
• 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	rs1438429191	0.092	None	N	0.123	0.14	0.0297737177859	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
E/D	rs1438429191	0.092	None	N	0.123	0.14	0.0297737177859	gnomAD-4.0.0	6.8472E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.15942E-05	0
E/K	rs1300968279	None	0.236	N	0.285	0.359	0.32980341726	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	2.42E-05	0	0	0	0	None	0	0	0	0	0
E/K	rs1300968279	None	0.236	N	0.285	0.359	0.32980341726	gnomAD-4.0.0	6.57583E-06	None	None	None	None	N	None	2.41546E-05	0	None	0	0	None	0	0	0	0	0
E/Q	rs1300968279	0.28	0.52	N	0.315	0.318	0.257292322809	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
E/Q	rs1300968279	0.28	0.52	N	0.315	0.318	0.257292322809	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	6.55E-05	0	0	0	None	0	0	0	0	0
E/Q	rs1300968279	0.28	0.52	N	0.315	0.318	0.257292322809	gnomAD-4.0.0	5.13343E-06	None	None	None	None	N	None	0	6.77897E-05	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	0.1723	likely_benign	0.2019	benign	-0.345	Destabilizing	0.002	N	0.183	neutral	N	0.463202388	None	None	N
E/C	0.8749	likely_pathogenic	0.9016	pathogenic	-0.012	Destabilizing	0.978	D	0.365	neutral	None	None	None	None	N
E/D	0.1	likely_benign	0.1174	benign	-0.265	Destabilizing	None	N	0.123	neutral	N	0.339483743	None	None	N
E/F	0.8479	likely_pathogenic	0.8866	pathogenic	-0.3	Destabilizing	0.955	D	0.387	neutral	None	None	None	None	N
E/G	0.0728	likely_benign	0.0711	benign	-0.551	Destabilizing	0.001	N	0.199	neutral	N	0.414619007	None	None	N
E/H	0.5699	likely_pathogenic	0.6492	pathogenic	-0.198	Destabilizing	0.939	D	0.281	neutral	None	None	None	None	N
E/I	0.7025	likely_pathogenic	0.7817	pathogenic	0.163	Stabilizing	0.767	D	0.417	neutral	None	None	None	None	N
E/K	0.2401	likely_benign	0.3057	benign	0.131	Stabilizing	0.236	N	0.285	neutral	N	0.459546007	None	None	N
E/L	0.5669	likely_pathogenic	0.649	pathogenic	0.163	Stabilizing	0.317	N	0.458	neutral	None	None	None	None	N
E/M	0.6372	likely_pathogenic	0.7091	pathogenic	0.279	Stabilizing	0.872	D	0.367	neutral	None	None	None	None	N
E/N	0.1972	likely_benign	0.2308	benign	0.001	Stabilizing	0.097	N	0.261	neutral	None	None	None	None	N
E/P	0.8825	likely_pathogenic	0.9069	pathogenic	0.014	Stabilizing	0.123	N	0.419	neutral	None	None	None	None	N
E/Q	0.1641	likely_benign	0.1896	benign	0.035	Stabilizing	0.52	D	0.315	neutral	N	0.495160091	None	None	N
E/R	0.3495	ambiguous	0.4195	ambiguous	0.314	Stabilizing	0.668	D	0.281	neutral	None	None	None	None	N
E/S	0.2054	likely_benign	0.2352	benign	-0.217	Destabilizing	0.099	N	0.289	neutral	None	None	None	None	N
E/T	0.4167	ambiguous	0.5106	ambiguous	-0.061	Destabilizing	0.425	N	0.393	neutral	None	None	None	None	N
E/V	0.4755	ambiguous	0.5719	pathogenic	0.014	Stabilizing	0.199	N	0.459	neutral	N	0.48265494	None	None	N
E/W	0.9315	likely_pathogenic	0.9497	pathogenic	-0.2	Destabilizing	0.995	D	0.379	neutral	None	None	None	None	N
E/Y	0.6736	likely_pathogenic	0.7416	pathogenic	-0.081	Destabilizing	0.983	D	0.381	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.