TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15413	46462;46463;46464	chr2:178620284;178620283;178620282	chr2:179485011;179485010;179485009
N2AB	13772	41539;41540;41541	chr2:178620284;178620283;178620282	chr2:179485011;179485010;179485009
N2A	12845	38758;38759;38760	chr2:178620284;178620283;178620282	chr2:179485011;179485010;179485009
N2B	6348	19267;19268;19269	chr2:178620284;178620283;178620282	chr2:179485011;179485010;179485009
Novex-1	6473	19642;19643;19644	chr2:178620284;178620283;178620282	chr2:179485011;179485010;179485009
Novex-2	6540	19843;19844;19845	chr2:178620284;178620283;178620282	chr2:179485011;179485010;179485009
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-106
• Domain position: 23
• Structural Position: 34
• Q(SASA): 0.2297
• 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/R	rs878864622	None	0.704	N	0.505	0.308	None	gnomAD-4.0.0	2.14504E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.77101E-06	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	0.3542	ambiguous	0.3834	ambiguous	-0.765	Destabilizing	0.863	D	0.48	neutral	None	None	None	None	N
Q/C	0.7338	likely_pathogenic	0.8088	pathogenic	-0.256	Destabilizing	0.999	D	0.613	neutral	None	None	None	None	N
Q/D	0.6947	likely_pathogenic	0.7777	pathogenic	-0.925	Destabilizing	0.759	D	0.5	neutral	None	None	None	None	N
Q/E	0.14	likely_benign	0.147	benign	-0.798	Destabilizing	0.021	N	0.147	neutral	N	0.380985487	None	None	N
Q/F	0.7428	likely_pathogenic	0.795	pathogenic	-0.44	Destabilizing	0.997	D	0.615	neutral	None	None	None	None	N
Q/G	0.5293	ambiguous	0.6139	pathogenic	-1.134	Destabilizing	0.969	D	0.577	neutral	None	None	None	None	N
Q/H	0.2728	likely_benign	0.3429	ambiguous	-0.943	Destabilizing	0.996	D	0.521	neutral	N	0.513326035	None	None	N
Q/I	0.4292	ambiguous	0.4942	ambiguous	0.187	Stabilizing	0.997	D	0.629	neutral	None	None	None	None	N
Q/K	0.1007	likely_benign	0.1164	benign	-0.387	Destabilizing	0.061	N	0.167	neutral	N	0.428417511	None	None	N
Q/L	0.2283	likely_benign	0.2761	benign	0.187	Stabilizing	0.959	D	0.589	neutral	N	0.514744982	None	None	N
Q/M	0.455	ambiguous	0.4881	ambiguous	0.608	Stabilizing	0.997	D	0.515	neutral	None	None	None	None	N
Q/N	0.4375	ambiguous	0.5238	ambiguous	-1.022	Destabilizing	0.969	D	0.493	neutral	None	None	None	None	N
Q/P	0.7626	likely_pathogenic	0.893	pathogenic	-0.1	Destabilizing	0.986	D	0.539	neutral	D	0.562697157	None	None	N
Q/R	0.1119	likely_benign	0.1309	benign	-0.33	Destabilizing	0.704	D	0.505	neutral	N	0.490068566	None	None	N
Q/S	0.354	ambiguous	0.3901	ambiguous	-1.164	Destabilizing	0.863	D	0.51	neutral	None	None	None	None	N
Q/T	0.2676	likely_benign	0.2874	benign	-0.842	Destabilizing	0.969	D	0.547	neutral	None	None	None	None	N
Q/V	0.3089	likely_benign	0.3417	ambiguous	-0.1	Destabilizing	0.969	D	0.561	neutral	None	None	None	None	N
Q/W	0.7636	likely_pathogenic	0.8152	pathogenic	-0.312	Destabilizing	0.999	D	0.59	neutral	None	None	None	None	N
Q/Y	0.5874	likely_pathogenic	0.6674	pathogenic	-0.054	Destabilizing	0.997	D	0.559	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.