TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5131	15616;15617;15618	chr2:178734433;178734432;178734431	chr2:179599160;179599159;179599158
N2AB	4814	14665;14666;14667	chr2:178734433;178734432;178734431	chr2:179599160;179599159;179599158
N2A	3887	11884;11885;11886	chr2:178734433;178734432;178734431	chr2:179599160;179599159;179599158
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: C
• RefSeq wild type transcript codon: TGT
• RefSeq wild type template codon: ACA
• Domain: Ig-34
• Domain position: 57
• Structural Position: 137
• Q(SASA): 0.119
• 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
C/Y	rs757766582	-1.126	None	N	0.365	0.083	0.207176502487	gnomAD-2.1.1	7.14E-06	None	None	None	None	N	None	4.13E-05	0	None	0	0	None	0	None	0	7.82E-06	0
C/Y	rs757766582	-1.126	None	N	0.365	0.083	0.207176502487	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	4.83E-05	0	0	0	0	None	0	0	0	0	0
C/Y	rs757766582	-1.126	None	N	0.365	0.083	0.207176502487	gnomAD-4.0.0	5.12468E-06	None	None	None	None	N	None	5.07374E-05	0	None	0	0	None	0	0	2.39318E-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
C/A	0.0963	likely_benign	0.1027	benign	-1.507	Destabilizing	None	N	0.3	neutral	None	None	None	None	N
C/D	0.2171	likely_benign	0.314	benign	-1.312	Destabilizing	0.002	N	0.57	neutral	None	None	None	None	N
C/E	0.3103	likely_benign	0.4391	ambiguous	-1.066	Destabilizing	0.001	N	0.596	neutral	None	None	None	None	N
C/F	0.0659	likely_benign	0.0767	benign	-0.881	Destabilizing	None	N	0.365	neutral	N	0.412902404	None	None	N
C/G	0.0757	likely_benign	0.0824	benign	-1.878	Destabilizing	0.001	N	0.56	neutral	N	0.447693779	None	None	N
C/H	0.1264	likely_benign	0.1603	benign	-2.037	Highly Destabilizing	0.021	N	0.633	neutral	None	None	None	None	N
C/I	0.1336	likely_benign	0.1768	benign	-0.498	Destabilizing	0.002	N	0.501	neutral	None	None	None	None	N
C/K	0.2816	likely_benign	0.3743	ambiguous	-0.871	Destabilizing	0.001	N	0.597	neutral	None	None	None	None	N
C/L	0.1471	likely_benign	0.1633	benign	-0.498	Destabilizing	0.001	N	0.44	neutral	None	None	None	None	N
C/M	0.2093	likely_benign	0.2345	benign	0.338	Stabilizing	0.041	N	0.613	neutral	None	None	None	None	N
C/N	0.1039	likely_benign	0.1299	benign	-1.547	Destabilizing	0.002	N	0.569	neutral	None	None	None	None	N
C/P	0.782	likely_pathogenic	0.8621	pathogenic	-0.812	Destabilizing	0.009	N	0.587	neutral	None	None	None	None	N
C/Q	0.1808	likely_benign	0.2426	benign	-1.048	Destabilizing	0.009	N	0.579	neutral	None	None	None	None	N
C/R	0.1554	likely_benign	0.2006	benign	-1.328	Destabilizing	None	N	0.457	neutral	N	0.361065431	None	None	N
C/S	0.0601	likely_benign	0.0628	benign	-1.841	Destabilizing	None	N	0.305	neutral	N	0.271500216	None	None	N
C/T	0.0899	likely_benign	0.1036	benign	-1.403	Destabilizing	0.001	N	0.527	neutral	None	None	None	None	N
C/V	0.1383	likely_benign	0.1655	benign	-0.812	Destabilizing	0.002	N	0.511	neutral	None	None	None	None	N
C/W	0.1747	likely_benign	0.2059	benign	-1.268	Destabilizing	0.103	N	0.62	neutral	N	0.497287217	None	None	N
C/Y	0.068	likely_benign	0.085	benign	-1.054	Destabilizing	None	N	0.365	neutral	N	0.38139852	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.