TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26930	81013;81014;81015	chr2:178565344;178565343;178565342	chr2:179430071;179430070;179430069
N2AB	25289	76090;76091;76092	chr2:178565344;178565343;178565342	chr2:179430071;179430070;179430069
N2A	24362	73309;73310;73311	chr2:178565344;178565343;178565342	chr2:179430071;179430070;179430069
N2B	17865	53818;53819;53820	chr2:178565344;178565343;178565342	chr2:179430071;179430070;179430069
Novex-1	17990	54193;54194;54195	chr2:178565344;178565343;178565342	chr2:179430071;179430070;179430069
Novex-2	18057	54394;54395;54396	chr2:178565344;178565343;178565342	chr2:179430071;179430070;179430069
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-139
• Domain position: 51
• Structural Position: 127
• Q(SASA): 0.375
• 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	None	0.005	N	0.366	0.14	0.28798054836	gnomAD-4.0.0	1.59158E-06	None	None	None	None	N	None	0	0	None	0	2.77316E-05	None	0	0	0	0	0
E/K	rs370511450	0.12	None	N	0.263	0.072	None	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.89E-06	0
E/K	rs370511450	0.12	None	N	0.263	0.072	None	gnomAD-3.1.2	1.32E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	2.94E-05	0	0
E/K	rs370511450	0.12	None	N	0.263	0.072	None	gnomAD-4.0.0	5.57803E-06	None	None	None	None	N	None	1.33547E-05	0	None	0	0	None	0	0	6.78151E-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	0.0998	likely_benign	0.1137	benign	-0.578	Destabilizing	0.005	N	0.366	neutral	N	0.454289329	None	None	N
E/C	0.5947	likely_pathogenic	0.6884	pathogenic	-0.061	Destabilizing	0.864	D	0.544	neutral	None	None	None	None	N
E/D	0.0955	likely_benign	0.0878	benign	-0.58	Destabilizing	None	N	0.259	neutral	N	0.408365039	None	None	N
E/F	0.5476	ambiguous	0.607	pathogenic	-0.426	Destabilizing	0.628	D	0.569	neutral	None	None	None	None	N
E/G	0.1069	likely_benign	0.1215	benign	-0.825	Destabilizing	0.012	N	0.501	neutral	N	0.446152636	None	None	N
E/H	0.287	likely_benign	0.346	ambiguous	-0.488	Destabilizing	0.356	N	0.418	neutral	None	None	None	None	N
E/I	0.187	likely_benign	0.24	benign	0.057	Stabilizing	0.072	N	0.583	neutral	None	None	None	None	N
E/K	0.0969	likely_benign	0.1358	benign	0.128	Stabilizing	None	N	0.263	neutral	N	0.428873597	None	None	N
E/L	0.239	likely_benign	0.2969	benign	0.057	Stabilizing	0.031	N	0.555	neutral	None	None	None	None	N
E/M	0.2605	likely_benign	0.3185	benign	0.343	Stabilizing	0.356	N	0.554	neutral	None	None	None	None	N
E/N	0.1153	likely_benign	0.1341	benign	-0.23	Destabilizing	None	N	0.253	neutral	None	None	None	None	N
E/P	0.3611	ambiguous	0.4323	ambiguous	-0.134	Destabilizing	0.136	N	0.496	neutral	None	None	None	None	N
E/Q	0.1038	likely_benign	0.1238	benign	-0.181	Destabilizing	0.001	N	0.265	neutral	N	0.457849709	None	None	N
E/R	0.1741	likely_benign	0.235	benign	0.26	Stabilizing	0.001	N	0.252	neutral	None	None	None	None	N
E/S	0.118	likely_benign	0.1285	benign	-0.414	Destabilizing	0.001	N	0.263	neutral	None	None	None	None	N
E/T	0.1037	likely_benign	0.1192	benign	-0.211	Destabilizing	None	N	0.315	neutral	None	None	None	None	N
E/V	0.1183	likely_benign	0.1426	benign	-0.134	Destabilizing	0.055	N	0.548	neutral	N	0.44784336	None	None	N
E/W	0.7638	likely_pathogenic	0.8247	pathogenic	-0.247	Destabilizing	0.864	D	0.551	neutral	None	None	None	None	N
E/Y	0.3898	ambiguous	0.4663	ambiguous	-0.176	Destabilizing	0.356	N	0.573	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.