TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7615	23068;23069;23070	chr2:178721176;178721175;178721174	chr2:179585903;179585902;179585901
N2AB	7298	22117;22118;22119	chr2:178721176;178721175;178721174	chr2:179585903;179585902;179585901
N2A	6371	19336;19337;19338	chr2:178721176;178721175;178721174	chr2:179585903;179585902;179585901
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-61
• Domain position: 8
• Structural Position: 9
• Q(SASA): 0.5944
• 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/D	rs1422183428	-0.012	None	N	0.12	0.068	0.136095386433	gnomAD-2.1.1	4.09E-06	None	None	None	None	N	None	0	2.95E-05	None	0	0	None	0	None	0	0	0
E/D	rs1422183428	-0.012	None	N	0.12	0.068	0.136095386433	gnomAD-4.0.0	1.62079E-06	None	None	None	None	N	None	0	2.32137E-05	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
E/A	0.1472	likely_benign	0.1222	benign	-0.112	Destabilizing	0.034	N	0.432	neutral	N	0.504290422	None	None	N
E/C	0.8679	likely_pathogenic	0.8049	pathogenic	0.056	Stabilizing	0.792	D	0.495	neutral	None	None	None	None	N
E/D	0.0933	likely_benign	0.0749	benign	-0.157	Destabilizing	None	N	0.12	neutral	N	0.487878175	None	None	N
E/F	0.775	likely_pathogenic	0.6857	pathogenic	-0.051	Destabilizing	0.381	N	0.479	neutral	None	None	None	None	N
E/G	0.1704	likely_benign	0.1312	benign	-0.278	Destabilizing	0.105	N	0.427	neutral	N	0.45703524	None	None	N
E/H	0.5057	ambiguous	0.3837	ambiguous	0.298	Stabilizing	None	N	0.259	neutral	None	None	None	None	N
E/I	0.4344	ambiguous	0.3566	ambiguous	0.275	Stabilizing	0.224	N	0.493	neutral	None	None	None	None	N
E/K	0.2456	likely_benign	0.1804	benign	0.566	Stabilizing	0.032	N	0.429	neutral	N	0.456880478	None	None	N
E/L	0.396	ambiguous	0.3098	benign	0.275	Stabilizing	0.125	N	0.482	neutral	None	None	None	None	N
E/M	0.5457	ambiguous	0.4663	ambiguous	0.232	Stabilizing	0.372	N	0.46	neutral	None	None	None	None	N
E/N	0.2631	likely_benign	0.1855	benign	0.259	Stabilizing	0.009	N	0.354	neutral	None	None	None	None	N
E/P	0.3478	ambiguous	0.2942	benign	0.166	Stabilizing	0.041	N	0.448	neutral	None	None	None	None	N
E/Q	0.1725	likely_benign	0.143	benign	0.3	Stabilizing	0.002	N	0.235	neutral	N	0.474620876	None	None	N
E/R	0.367	ambiguous	0.2829	benign	0.725	Stabilizing	0.08	N	0.389	neutral	None	None	None	None	N
E/S	0.202	likely_benign	0.1592	benign	0.116	Stabilizing	0.023	N	0.39	neutral	None	None	None	None	N
E/T	0.2546	likely_benign	0.2084	benign	0.26	Stabilizing	0.061	N	0.436	neutral	None	None	None	None	N
E/V	0.2341	likely_benign	0.1921	benign	0.166	Stabilizing	0.134	N	0.465	neutral	N	0.512448546	None	None	N
E/W	0.9044	likely_pathogenic	0.8453	pathogenic	0.048	Stabilizing	0.95	D	0.551	neutral	None	None	None	None	N
E/Y	0.6731	likely_pathogenic	0.5444	ambiguous	0.191	Stabilizing	0.448	N	0.487	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.