TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27229	81910;81911;81912	chr2:178564447;178564446;178564445	chr2:179429174;179429173;179429172
N2AB	25588	76987;76988;76989	chr2:178564447;178564446;178564445	chr2:179429174;179429173;179429172
N2A	24661	74206;74207;74208	chr2:178564447;178564446;178564445	chr2:179429174;179429173;179429172
N2B	18164	54715;54716;54717	chr2:178564447;178564446;178564445	chr2:179429174;179429173;179429172
Novex-1	18289	55090;55091;55092	chr2:178564447;178564446;178564445	chr2:179429174;179429173;179429172
Novex-2	18356	55291;55292;55293	chr2:178564447;178564446;178564445	chr2:179429174;179429173;179429172
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: Fn3-86
• Domain position: 60
• Structural Position: 90
• Q(SASA): 0.5054
• 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/K	None	None	0.309	N	0.399	0.227	0.193865811164	gnomAD-4.0.0	1.59442E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43414E-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	0.1506	likely_benign	0.1473	benign	-0.703	Destabilizing	0.472	N	0.407	neutral	N	0.474344022	None	None	N
E/C	0.7531	likely_pathogenic	0.7645	pathogenic	-0.397	Destabilizing	0.996	D	0.609	neutral	None	None	None	None	N
E/D	0.2363	likely_benign	0.2271	benign	-0.969	Destabilizing	0.684	D	0.381	neutral	N	0.474282074	None	None	N
E/F	0.7075	likely_pathogenic	0.6944	pathogenic	0.101	Stabilizing	0.91	D	0.587	neutral	None	None	None	None	N
E/G	0.3023	likely_benign	0.2837	benign	-1.092	Destabilizing	0.684	D	0.52	neutral	N	0.473775095	None	None	N
E/H	0.4157	ambiguous	0.4131	ambiguous	None	Stabilizing	0.953	D	0.474	neutral	None	None	None	None	N
E/I	0.2981	likely_benign	0.2855	benign	0.363	Stabilizing	0.835	D	0.583	neutral	None	None	None	None	N
E/K	0.2072	likely_benign	0.2034	benign	-0.339	Destabilizing	0.309	N	0.399	neutral	N	0.50027983	None	None	N
E/L	0.4732	ambiguous	0.4298	ambiguous	0.363	Stabilizing	0.59	D	0.488	neutral	None	None	None	None	N
E/M	0.3965	ambiguous	0.3794	ambiguous	0.675	Stabilizing	0.206	N	0.455	neutral	None	None	None	None	N
E/N	0.2684	likely_benign	0.2606	benign	-1.014	Destabilizing	0.742	D	0.418	neutral	None	None	None	None	N
E/P	0.9767	likely_pathogenic	0.9742	pathogenic	0.03	Stabilizing	0.953	D	0.545	neutral	None	None	None	None	N
E/Q	0.1318	likely_benign	0.1341	benign	-0.848	Destabilizing	0.012	N	0.239	neutral	N	0.440674166	None	None	N
E/R	0.3345	likely_benign	0.3283	benign	0.021	Stabilizing	0.59	D	0.376	neutral	None	None	None	None	N
E/S	0.1738	likely_benign	0.1708	benign	-1.311	Destabilizing	0.742	D	0.361	neutral	None	None	None	None	N
E/T	0.1589	likely_benign	0.1601	benign	-0.975	Destabilizing	0.742	D	0.441	neutral	None	None	None	None	N
E/V	0.1781	likely_benign	0.1757	benign	0.03	Stabilizing	0.521	D	0.492	neutral	N	0.514537206	None	None	N
E/W	0.9015	likely_pathogenic	0.8972	pathogenic	0.423	Stabilizing	0.996	D	0.609	neutral	None	None	None	None	N
E/Y	0.5789	likely_pathogenic	0.5698	pathogenic	0.395	Stabilizing	0.984	D	0.576	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.