TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6902	20929;20930;20931	chr2:178725500;178725499;178725498	chr2:179590227;179590226;179590225
N2AB	6585	19978;19979;19980	chr2:178725500;178725499;178725498	chr2:179590227;179590226;179590225
N2A	5658	17197;17198;17199	chr2:178725500;178725499;178725498	chr2:179590227;179590226;179590225
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: R
• RefSeq wild type transcript codon: AGG
• RefSeq wild type template codon: TCC
• Domain: Ig-53
• Domain position: 49
• Structural Position: 122
• Q(SASA): 0.2988
• 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
R/K	None	None	0.001	N	0.118	0.096	0.181679512989	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
R/M	rs2079182473	None	0.963	N	0.395	0.479	0.444305618086	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
R/M	rs2079182473	None	0.963	N	0.395	0.479	0.444305618086	gnomAD-4.0.0	6.57324E-06	None	None	None	None	N	None	2.41313E-05	0	None	0	0	None	0	0	0	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
R/A	0.2414	likely_benign	0.2392	benign	-0.275	Destabilizing	0.25	N	0.321	neutral	None	None	None	None	N
R/C	0.1779	likely_benign	0.1642	benign	-0.269	Destabilizing	0.992	D	0.43	neutral	None	None	None	None	N
R/D	0.4491	ambiguous	0.4421	ambiguous	-0.008	Destabilizing	0.617	D	0.386	neutral	None	None	None	None	N
R/E	0.23	likely_benign	0.2217	benign	0.077	Stabilizing	0.25	N	0.274	neutral	None	None	None	None	N
R/F	0.3731	ambiguous	0.3472	ambiguous	-0.343	Destabilizing	0.92	D	0.44	neutral	None	None	None	None	N
R/G	0.1688	likely_benign	0.1705	benign	-0.527	Destabilizing	0.549	D	0.381	neutral	N	0.499090231	None	None	N
R/H	0.0836	likely_benign	0.078	benign	-0.949	Destabilizing	0.92	D	0.363	neutral	None	None	None	None	N
R/I	0.1822	likely_benign	0.1788	benign	0.371	Stabilizing	0.85	D	0.44	neutral	None	None	None	None	N
R/K	0.0876	likely_benign	0.0796	benign	-0.317	Destabilizing	0.001	N	0.118	neutral	N	0.466082404	None	None	N
R/L	0.1886	likely_benign	0.1843	benign	0.371	Stabilizing	0.447	N	0.389	neutral	None	None	None	None	N
R/M	0.1913	likely_benign	0.1841	benign	0.023	Stabilizing	0.963	D	0.395	neutral	N	0.492342282	None	None	N
R/N	0.33	likely_benign	0.319	benign	0.119	Stabilizing	0.617	D	0.239	neutral	None	None	None	None	N
R/P	0.8184	likely_pathogenic	0.85	pathogenic	0.177	Stabilizing	0.766	D	0.423	neutral	None	None	None	None	N
R/Q	0.0859	likely_benign	0.0803	benign	-0.05	Destabilizing	0.059	N	0.193	neutral	None	None	None	None	N
R/S	0.248	likely_benign	0.2451	benign	-0.428	Destabilizing	0.201	N	0.315	neutral	N	0.487055109	None	None	N
R/T	0.1354	likely_benign	0.1281	benign	-0.187	Destabilizing	0.016	N	0.22	neutral	N	0.483246799	None	None	N
R/V	0.2438	likely_benign	0.2315	benign	0.177	Stabilizing	0.447	N	0.413	neutral	None	None	None	None	N
R/W	0.1256	likely_benign	0.1193	benign	-0.211	Destabilizing	0.99	D	0.444	neutral	N	0.472339159	None	None	N
R/Y	0.27	likely_benign	0.2449	benign	0.154	Stabilizing	0.972	D	0.423	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.