TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2321	7186;7187;7188	chr2:178774303;178774302;178774301	chr2:179639030;179639029;179639028
N2AB	2321	7186;7187;7188	chr2:178774303;178774302;178774301	chr2:179639030;179639029;179639028
N2A	2321	7186;7187;7188	chr2:178774303;178774302;178774301	chr2:179639030;179639029;179639028
N2B	2275	7048;7049;7050	chr2:178774303;178774302;178774301	chr2:179639030;179639029;179639028
Novex-1	2275	7048;7049;7050	chr2:178774303;178774302;178774301	chr2:179639030;179639029;179639028
Novex-2	2275	7048;7049;7050	chr2:178774303;178774302;178774301	chr2:179639030;179639029;179639028
Novex-3	2321	7186;7187;7188	chr2:178774303;178774302;178774301	chr2:179639030;179639029;179639028

Information

• RefSeq wild type amino acid: Q
• RefSeq wild type transcript codon: CAG
• RefSeq wild type template codon: GTC
• Domain: Ig-12
• Domain position: 55
• Structural Position: 136
• Q(SASA): 0.1779
• 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
Q/K	None	None	0.454	N	0.603	0.349	0.117506650769	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	6.33473E-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
Q/A	0.4963	ambiguous	0.4683	ambiguous	-1.238	Destabilizing	0.688	D	0.697	prob.neutral	None	None	None	None	N
Q/C	0.6312	likely_pathogenic	0.5998	pathogenic	-0.936	Destabilizing	0.998	D	0.749	deleterious	None	None	None	None	N
Q/D	0.8364	likely_pathogenic	0.7966	pathogenic	-2.323	Highly Destabilizing	0.915	D	0.671	neutral	None	None	None	None	N
Q/E	0.1943	likely_benign	0.1809	benign	-1.994	Destabilizing	0.625	D	0.542	neutral	N	0.447361167	None	None	N
Q/F	0.7228	likely_pathogenic	0.6808	pathogenic	-0.913	Destabilizing	0.974	D	0.783	deleterious	None	None	None	None	N
Q/G	0.629	likely_pathogenic	0.5903	pathogenic	-1.673	Destabilizing	0.915	D	0.733	prob.delet.	None	None	None	None	N
Q/H	0.2229	likely_benign	0.1971	benign	-1.434	Destabilizing	0.005	N	0.391	neutral	N	0.28588478	None	None	N
Q/I	0.5014	ambiguous	0.481	ambiguous	-0.036	Destabilizing	0.974	D	0.787	deleterious	None	None	None	None	N
Q/K	0.2007	likely_benign	0.1894	benign	-0.426	Destabilizing	0.454	N	0.603	neutral	N	0.431244944	None	None	N
Q/L	0.235	likely_benign	0.2149	benign	-0.036	Destabilizing	0.801	D	0.735	prob.delet.	N	0.412228676	None	None	N
Q/M	0.4616	ambiguous	0.4472	ambiguous	-0.022	Destabilizing	0.991	D	0.729	prob.delet.	None	None	None	None	N
Q/N	0.4897	ambiguous	0.4403	ambiguous	-1.414	Destabilizing	0.842	D	0.664	neutral	None	None	None	None	N
Q/P	0.8886	likely_pathogenic	0.8482	pathogenic	-0.414	Destabilizing	0.989	D	0.749	deleterious	N	0.447361167	None	None	N
Q/R	0.1853	likely_benign	0.1701	benign	-0.785	Destabilizing	0.012	N	0.451	neutral	N	0.381442879	None	None	N
Q/S	0.5328	ambiguous	0.4998	ambiguous	-1.653	Destabilizing	0.688	D	0.629	neutral	None	None	None	None	N
Q/T	0.4372	ambiguous	0.4058	ambiguous	-1.141	Destabilizing	0.915	D	0.719	prob.delet.	None	None	None	None	N
Q/V	0.3682	ambiguous	0.3599	ambiguous	-0.414	Destabilizing	0.915	D	0.74	deleterious	None	None	None	None	N
Q/W	0.6449	likely_pathogenic	0.6014	pathogenic	-1.109	Destabilizing	0.998	D	0.715	prob.delet.	None	None	None	None	N
Q/Y	0.4475	ambiguous	0.4003	ambiguous	-0.643	Destabilizing	0.842	D	0.724	prob.delet.	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.