TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22633	68122;68123;68124	chr2:178579133;178579132;178579131	chr2:179443860;179443859;179443858
N2AB	20992	63199;63200;63201	chr2:178579133;178579132;178579131	chr2:179443860;179443859;179443858
N2A	20065	60418;60419;60420	chr2:178579133;178579132;178579131	chr2:179443860;179443859;179443858
N2B	13568	40927;40928;40929	chr2:178579133;178579132;178579131	chr2:179443860;179443859;179443858
Novex-1	13693	41302;41303;41304	chr2:178579133;178579132;178579131	chr2:179443860;179443859;179443858
Novex-2	13760	41503;41504;41505	chr2:178579133;178579132;178579131	chr2:179443860;179443859;179443858
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-127
• Domain position: 74
• Structural Position: 168
• Q(SASA): 0.6913
• 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/K	None	None	0.994	N	0.581	0.441	0.564725595184	gnomAD-4.0.0	1.59204E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.43291E-05	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	0.168	likely_benign	0.1552	benign	-0.465	Destabilizing	0.994	D	0.615	neutral	N	0.521325185	None	None	I
E/C	0.879	likely_pathogenic	0.8775	pathogenic	0.011	Stabilizing	1.0	D	0.768	deleterious	None	None	None	None	I
E/D	0.2124	likely_benign	0.1858	benign	-0.414	Destabilizing	0.104	N	0.245	neutral	N	0.492042428	None	None	I
E/F	0.8679	likely_pathogenic	0.8482	pathogenic	-0.382	Destabilizing	1.0	D	0.71	prob.delet.	None	None	None	None	I
E/G	0.263	likely_benign	0.235	benign	-0.67	Destabilizing	0.994	D	0.583	neutral	N	0.50642452	None	None	I
E/H	0.6237	likely_pathogenic	0.5999	pathogenic	-0.264	Destabilizing	1.0	D	0.672	neutral	None	None	None	None	I
E/I	0.4237	ambiguous	0.402	ambiguous	0.042	Stabilizing	1.0	D	0.722	prob.delet.	None	None	None	None	I
E/K	0.2759	likely_benign	0.248	benign	0.317	Stabilizing	0.994	D	0.581	neutral	N	0.504123504	None	None	I
E/L	0.5696	likely_pathogenic	0.5383	ambiguous	0.042	Stabilizing	1.0	D	0.708	prob.delet.	None	None	None	None	I
E/M	0.5104	ambiguous	0.497	ambiguous	0.23	Stabilizing	1.0	D	0.686	prob.neutral	None	None	None	None	I
E/N	0.3948	ambiguous	0.3614	ambiguous	0.001	Stabilizing	0.998	D	0.661	neutral	None	None	None	None	I
E/P	0.9127	likely_pathogenic	0.887	pathogenic	-0.107	Destabilizing	1.0	D	0.68	prob.neutral	None	None	None	None	I
E/Q	0.1786	likely_benign	0.1723	benign	0.025	Stabilizing	0.998	D	0.637	neutral	N	0.520978468	None	None	I
E/R	0.459	ambiguous	0.432	ambiguous	0.461	Stabilizing	0.999	D	0.701	prob.neutral	None	None	None	None	I
E/S	0.2202	likely_benign	0.2095	benign	-0.16	Destabilizing	0.992	D	0.582	neutral	None	None	None	None	I
E/T	0.1648	likely_benign	0.1618	benign	0.007	Stabilizing	0.999	D	0.639	neutral	None	None	None	None	I
E/V	0.2181	likely_benign	0.2027	benign	-0.107	Destabilizing	0.999	D	0.683	prob.neutral	D	0.530003383	None	None	I
E/W	0.9529	likely_pathogenic	0.9473	pathogenic	-0.225	Destabilizing	1.0	D	0.766	deleterious	None	None	None	None	I
E/Y	0.796	likely_pathogenic	0.7673	pathogenic	-0.133	Destabilizing	1.0	D	0.695	prob.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.