TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27512	82759;82760;82761	chr2:178563598;178563597;178563596	chr2:179428325;179428324;179428323
N2AB	25871	77836;77837;77838	chr2:178563598;178563597;178563596	chr2:179428325;179428324;179428323
N2A	24944	75055;75056;75057	chr2:178563598;178563597;178563596	chr2:179428325;179428324;179428323
N2B	18447	55564;55565;55566	chr2:178563598;178563597;178563596	chr2:179428325;179428324;179428323
Novex-1	18572	55939;55940;55941	chr2:178563598;178563597;178563596	chr2:179428325;179428324;179428323
Novex-2	18639	56140;56141;56142	chr2:178563598;178563597;178563596	chr2:179428325;179428324;179428323
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: Fn3-88
• Domain position: 44
• Structural Position: 54
• Q(SASA): 0.7767
• 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	0.001	N	0.265	0.128	0.246215685461	gnomAD-4.0.0	1.59126E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43275E-05	0
E/K	None	None	0.175	N	0.309	0.166	0.249502417897	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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	0.1402	likely_benign	0.1496	benign	-0.153	Destabilizing	0.001	N	0.265	neutral	N	0.489044116	None	None	N
E/C	0.8175	likely_pathogenic	0.8224	pathogenic	-0.143	Destabilizing	0.883	D	0.241	neutral	None	None	None	None	N
E/D	0.088	likely_benign	0.1015	benign	-0.054	Destabilizing	None	N	0.183	neutral	N	0.414698286	None	None	N
E/F	0.7569	likely_pathogenic	0.7586	pathogenic	-0.212	Destabilizing	0.667	D	0.266	neutral	None	None	None	None	N
E/G	0.1612	likely_benign	0.1883	benign	-0.277	Destabilizing	None	N	0.229	neutral	N	0.434668127	None	None	N
E/H	0.4991	ambiguous	0.5095	ambiguous	0.318	Stabilizing	0.859	D	0.264	neutral	None	None	None	None	N
E/I	0.4644	ambiguous	0.4294	ambiguous	0.122	Stabilizing	0.497	N	0.313	neutral	None	None	None	None	N
E/K	0.2645	likely_benign	0.2687	benign	0.266	Stabilizing	0.175	N	0.309	neutral	N	0.428457017	None	None	N
E/L	0.4183	ambiguous	0.4382	ambiguous	0.122	Stabilizing	0.124	N	0.329	neutral	None	None	None	None	N
E/M	0.5014	ambiguous	0.4887	ambiguous	-0.016	Destabilizing	0.958	D	0.259	neutral	None	None	None	None	N
E/N	0.2242	likely_benign	0.24	benign	0.229	Stabilizing	0.124	N	0.281	neutral	None	None	None	None	N
E/P	0.7774	likely_pathogenic	0.8087	pathogenic	0.048	Stabilizing	0.364	N	0.334	neutral	None	None	None	None	N
E/Q	0.2007	likely_benign	0.2054	benign	0.23	Stabilizing	0.175	N	0.303	neutral	N	0.505859008	None	None	N
E/R	0.3654	ambiguous	0.3779	ambiguous	0.512	Stabilizing	0.497	N	0.275	neutral	None	None	None	None	N
E/S	0.1763	likely_benign	0.1957	benign	-0.005	Destabilizing	0.055	N	0.339	neutral	None	None	None	None	N
E/T	0.2063	likely_benign	0.2064	benign	0.095	Stabilizing	0.001	N	0.295	neutral	None	None	None	None	N
E/V	0.2591	likely_benign	0.2504	benign	0.048	Stabilizing	0.096	N	0.335	neutral	N	0.49972247	None	None	N
E/W	0.8799	likely_pathogenic	0.8863	pathogenic	-0.156	Destabilizing	0.958	D	0.286	neutral	None	None	None	None	N
E/Y	0.5743	likely_pathogenic	0.5762	pathogenic	0.007	Stabilizing	0.859	D	0.28	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.