TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9266	28021;28022;28023	chr2:178712034;178712033;178712032	chr2:179576761;179576760;179576759
N2AB	8949	27070;27071;27072	chr2:178712034;178712033;178712032	chr2:179576761;179576760;179576759
N2A	8022	24289;24290;24291	chr2:178712034;178712033;178712032	chr2:179576761;179576760;179576759
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: Q
• RefSeq wild type transcript codon: CAG
• RefSeq wild type template codon: GTC
• Domain: Ig-78
• Domain position: 62
• Structural Position: 143
• Q(SASA): 0.7887
• 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/H	rs543197876	None	0.996	N	0.329	0.185	0.132336055621	gnomAD-4.0.0	4.78964E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	6.29647E-06	0	0
Q/L	None	None	0.959	N	0.391	0.257	0.415947407303	gnomAD-4.0.0	1.59135E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.02425E-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
Q/A	0.2215	likely_benign	0.2447	benign	-0.2	Destabilizing	0.863	D	0.36	neutral	None	None	None	None	N
Q/C	0.6394	likely_pathogenic	0.6776	pathogenic	0.354	Stabilizing	0.999	D	0.363	neutral	None	None	None	None	N
Q/D	0.2939	likely_benign	0.3524	ambiguous	-0.073	Destabilizing	0.969	D	0.336	neutral	None	None	None	None	N
Q/E	0.08	likely_benign	0.0926	benign	-0.118	Destabilizing	0.826	D	0.346	neutral	N	0.387135178	None	None	N
Q/F	0.6679	likely_pathogenic	0.6843	pathogenic	-0.496	Destabilizing	0.997	D	0.355	neutral	None	None	None	None	N
Q/G	0.2584	likely_benign	0.3054	benign	-0.369	Destabilizing	0.969	D	0.391	neutral	None	None	None	None	N
Q/H	0.1643	likely_benign	0.1825	benign	-0.405	Destabilizing	0.996	D	0.329	neutral	N	0.42946459	None	None	N
Q/I	0.403	ambiguous	0.4342	ambiguous	0.151	Stabilizing	0.997	D	0.369	neutral	None	None	None	None	N
Q/K	0.0706	likely_benign	0.0749	benign	0.198	Stabilizing	0.021	N	0.149	neutral	N	0.365162395	None	None	N
Q/L	0.168	likely_benign	0.1888	benign	0.151	Stabilizing	0.959	D	0.391	neutral	N	0.482066924	None	None	N
Q/M	0.385	ambiguous	0.3937	ambiguous	0.573	Stabilizing	0.997	D	0.335	neutral	None	None	None	None	N
Q/N	0.2398	likely_benign	0.251	benign	-0.04	Destabilizing	0.969	D	0.328	neutral	None	None	None	None	N
Q/P	0.3445	ambiguous	0.4836	ambiguous	0.061	Stabilizing	0.986	D	0.36	neutral	N	0.436390562	None	None	N
Q/R	0.0768	likely_benign	0.0869	benign	0.342	Stabilizing	0.704	D	0.365	neutral	N	0.426346927	None	None	N
Q/S	0.2567	likely_benign	0.2649	benign	-0.054	Destabilizing	0.863	D	0.335	neutral	None	None	None	None	N
Q/T	0.1812	likely_benign	0.1955	benign	0.048	Stabilizing	0.969	D	0.365	neutral	None	None	None	None	N
Q/V	0.2875	likely_benign	0.3045	benign	0.061	Stabilizing	0.969	D	0.413	neutral	None	None	None	None	N
Q/W	0.517	ambiguous	0.6164	pathogenic	-0.478	Destabilizing	0.999	D	0.395	neutral	None	None	None	None	N
Q/Y	0.4176	ambiguous	0.449	ambiguous	-0.206	Destabilizing	0.997	D	0.331	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.