TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6892	20899;20900;20901	chr2:178725530;178725529;178725528	chr2:179590257;179590256;179590255
N2AB	6575	19948;19949;19950	chr2:178725530;178725529;178725528	chr2:179590257;179590256;179590255
N2A	5648	17167;17168;17169	chr2:178725530;178725529;178725528	chr2:179590257;179590256;179590255
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: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-53
• Domain position: 39
• Structural Position: 55
• Q(SASA): 0.4963
• 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	rs185833299	-0.048	0.978	N	0.417	0.341	None	gnomAD-2.1.1	2.14E-05	None	None	None	None	N	None	2.06954E-04	2.84E-05	None	0	0	None	0	None	0	0	0
E/K	rs185833299	-0.048	0.978	N	0.417	0.341	None	gnomAD-3.1.2	3.29E-05	None	None	None	None	N	None	9.65E-05	6.55E-05	0	0	0	None	0	0	0	0	0
E/K	rs185833299	-0.048	0.978	N	0.417	0.341	None	1000 genomes	1.99681E-04	None	None	None	None	N	None	0	1.4E-03	None	None	0	0	None	None	None	0	None
E/K	rs185833299	-0.048	0.978	N	0.417	0.341	None	gnomAD-4.0.0	7.43852E-06	None	None	None	None	N	None	1.33344E-04	1.66811E-05	None	0	0	None	0	0	0	0	1.60108E-05

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	0.1481	likely_benign	0.1551	benign	-0.127	Destabilizing	0.989	D	0.381	neutral	N	0.50643309	None	None	N
E/C	0.8159	likely_pathogenic	0.8262	pathogenic	-0.236	Destabilizing	1.0	D	0.591	neutral	None	None	None	None	N
E/D	0.1121	likely_benign	0.0969	benign	-0.262	Destabilizing	0.054	N	0.186	neutral	N	0.465178327	None	None	N
E/F	0.7005	likely_pathogenic	0.7457	pathogenic	-0.03	Destabilizing	0.999	D	0.559	neutral	None	None	None	None	N
E/G	0.0748	likely_benign	0.0776	benign	-0.276	Destabilizing	0.978	D	0.393	neutral	N	0.425926505	None	None	N
E/H	0.4917	ambiguous	0.5213	ambiguous	0.536	Stabilizing	0.999	D	0.363	neutral	None	None	None	None	N
E/I	0.4054	ambiguous	0.4472	ambiguous	0.219	Stabilizing	0.999	D	0.541	neutral	None	None	None	None	N
E/K	0.1635	likely_benign	0.1975	benign	0.397	Stabilizing	0.978	D	0.417	neutral	N	0.475648823	None	None	N
E/L	0.4042	ambiguous	0.4317	ambiguous	0.219	Stabilizing	0.998	D	0.525	neutral	None	None	None	None	N
E/M	0.4661	ambiguous	0.4947	ambiguous	0.011	Stabilizing	1.0	D	0.479	neutral	None	None	None	None	N
E/N	0.2061	likely_benign	0.1865	benign	0.033	Stabilizing	0.983	D	0.355	neutral	None	None	None	None	N
E/P	0.6176	likely_pathogenic	0.6522	pathogenic	0.122	Stabilizing	0.999	D	0.393	neutral	None	None	None	None	N
E/Q	0.1531	likely_benign	0.1709	benign	0.072	Stabilizing	0.989	D	0.394	neutral	N	0.493599866	None	None	N
E/R	0.2747	likely_benign	0.327	benign	0.681	Stabilizing	0.998	D	0.359	neutral	None	None	None	None	N
E/S	0.1817	likely_benign	0.1784	benign	-0.101	Destabilizing	0.983	D	0.376	neutral	None	None	None	None	N
E/T	0.2044	likely_benign	0.2103	benign	0.031	Stabilizing	0.992	D	0.367	neutral	None	None	None	None	N
E/V	0.2222	likely_benign	0.2634	benign	0.122	Stabilizing	0.999	D	0.415	neutral	N	0.504432935	None	None	N
E/W	0.8163	likely_pathogenic	0.85	pathogenic	0.071	Stabilizing	1.0	D	0.599	neutral	None	None	None	None	N
E/Y	0.5408	ambiguous	0.5661	pathogenic	0.203	Stabilizing	0.999	D	0.484	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.