TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8139	24640;24641;24642	chr2:178718785;178718784;178718783	chr2:179583512;179583511;179583510
N2AB	7822	23689;23690;23691	chr2:178718785;178718784;178718783	chr2:179583512;179583511;179583510
N2A	6895	20908;20909;20910	chr2:178718785;178718784;178718783	chr2:179583512;179583511;179583510
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: GAG
• RefSeq wild type template codon: CTC
• Domain: Ig-66
• Domain position: 62
• Structural Position: 143
• Q(SASA): 0.7376
• Predicted PPI site: I

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/Q	rs1202623297	0.392	0.175	N	0.237	0.091	0.132336055621	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.89E-06	0
E/Q	rs1202623297	0.392	0.175	N	0.237	0.091	0.132336055621	gnomAD-4.0.0	3.42108E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	4.49739E-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	0.1235	likely_benign	0.1244	benign	-0.551	Destabilizing	0.001	N	0.126	neutral	N	0.488974253	None	None	I
E/C	0.7126	likely_pathogenic	0.6902	pathogenic	-0.027	Destabilizing	0.958	D	0.247	neutral	None	None	None	None	I
E/D	0.0887	likely_benign	0.0826	benign	-0.291	Destabilizing	None	N	0.088	neutral	N	0.422882547	None	None	I
E/F	0.5734	likely_pathogenic	0.5906	pathogenic	-0.45	Destabilizing	0.859	D	0.285	neutral	None	None	None	None	I
E/G	0.1156	likely_benign	0.1146	benign	-0.736	Destabilizing	0.042	N	0.221	neutral	N	0.494110714	None	None	I
E/H	0.2447	likely_benign	0.2342	benign	-0.277	Destabilizing	0.667	D	0.219	neutral	None	None	None	None	I
E/I	0.3557	ambiguous	0.3891	ambiguous	-0.097	Destabilizing	0.364	N	0.35	neutral	None	None	None	None	I
E/K	0.1006	likely_benign	0.1053	benign	0.336	Stabilizing	0.001	N	0.129	neutral	N	0.464249167	None	None	I
E/L	0.2962	likely_benign	0.3069	benign	-0.097	Destabilizing	0.22	N	0.316	neutral	None	None	None	None	I
E/M	0.3838	ambiguous	0.3961	ambiguous	0.109	Stabilizing	0.859	D	0.266	neutral	None	None	None	None	I
E/N	0.1416	likely_benign	0.1371	benign	-0.009	Destabilizing	None	N	0.101	neutral	None	None	None	None	I
E/P	0.539	ambiguous	0.5419	ambiguous	-0.23	Destabilizing	0.364	N	0.305	neutral	None	None	None	None	I
E/Q	0.0989	likely_benign	0.0986	benign	0.022	Stabilizing	0.175	N	0.237	neutral	N	0.480528128	None	None	I
E/R	0.141	likely_benign	0.1471	benign	0.469	Stabilizing	0.124	N	0.151	neutral	None	None	None	None	I
E/S	0.1264	likely_benign	0.1265	benign	-0.16	Destabilizing	0.005	N	0.134	neutral	None	None	None	None	I
E/T	0.184	likely_benign	0.1927	benign	-0.002	Destabilizing	0.055	N	0.252	neutral	None	None	None	None	I
E/V	0.2244	likely_benign	0.2481	benign	-0.23	Destabilizing	0.175	N	0.289	neutral	N	0.475215174	None	None	I
E/W	0.7325	likely_pathogenic	0.7378	pathogenic	-0.275	Destabilizing	0.958	D	0.261	neutral	None	None	None	None	I
E/Y	0.4079	ambiguous	0.4177	ambiguous	-0.207	Destabilizing	0.859	D	0.277	neutral	None	None	None	None	I

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.