TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6270	19033;19034;19035	chr2:178729348;178729347;178729346	chr2:179594075;179594074;179594073
N2AB	5953	18082;18083;18084	chr2:178729348;178729347;178729346	chr2:179594075;179594074;179594073
N2A	5026	15301;15302;15303	chr2:178729348;178729347;178729346	chr2:179594075;179594074;179594073
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-46
• Domain position: 72
• Structural Position: 155
• Q(SASA): 0.1925
• 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/P	None	None	0.999	N	0.621	0.378	0.430126000877	gnomAD-4.0.0	1.59194E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85968E-06	0	0
Q/R	None	None	0.997	N	0.537	0.205	0.18274738541	gnomAD-4.0.0	1.59194E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85968E-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	0.3447	ambiguous	0.3441	ambiguous	-0.756	Destabilizing	0.964	D	0.585	neutral	None	None	None	None	N
Q/C	0.6674	likely_pathogenic	0.6959	pathogenic	-0.479	Destabilizing	1.0	D	0.76	deleterious	None	None	None	None	N
Q/D	0.6341	likely_pathogenic	0.6601	pathogenic	-1.459	Destabilizing	0.998	D	0.507	neutral	None	None	None	None	N
Q/E	0.111	likely_benign	0.1114	benign	-1.296	Destabilizing	0.992	D	0.589	neutral	N	0.482720285	None	None	N
Q/F	0.743	likely_pathogenic	0.7597	pathogenic	-0.539	Destabilizing	0.998	D	0.769	deleterious	None	None	None	None	N
Q/G	0.4509	ambiguous	0.4584	ambiguous	-1.133	Destabilizing	0.998	D	0.605	neutral	None	None	None	None	N
Q/H	0.2287	likely_benign	0.2441	benign	-1.004	Destabilizing	0.999	D	0.54	neutral	N	0.469833123	None	None	N
Q/I	0.4074	ambiguous	0.4324	ambiguous	0.224	Stabilizing	0.971	D	0.651	neutral	None	None	None	None	N
Q/K	0.1231	likely_benign	0.1162	benign	-0.327	Destabilizing	0.997	D	0.587	neutral	N	0.493417281	None	None	N
Q/L	0.1853	likely_benign	0.2051	benign	0.224	Stabilizing	0.961	D	0.625	neutral	N	0.451689188	None	None	N
Q/M	0.4083	ambiguous	0.4352	ambiguous	0.616	Stabilizing	0.998	D	0.535	neutral	None	None	None	None	N
Q/N	0.4188	ambiguous	0.4618	ambiguous	-1.105	Destabilizing	0.999	D	0.507	neutral	None	None	None	None	N
Q/P	0.909	likely_pathogenic	0.9259	pathogenic	-0.073	Destabilizing	0.999	D	0.621	neutral	N	0.504320113	None	None	N
Q/R	0.118	likely_benign	0.1129	benign	-0.325	Destabilizing	0.997	D	0.537	neutral	N	0.510136172	None	None	N
Q/S	0.327	likely_benign	0.3425	ambiguous	-1.234	Destabilizing	0.993	D	0.512	neutral	None	None	None	None	N
Q/T	0.2043	likely_benign	0.2167	benign	-0.873	Destabilizing	0.985	D	0.535	neutral	None	None	None	None	N
Q/V	0.2993	likely_benign	0.3111	benign	-0.073	Destabilizing	0.469	N	0.544	neutral	None	None	None	None	N
Q/W	0.6465	likely_pathogenic	0.6534	pathogenic	-0.468	Destabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	N
Q/Y	0.5184	ambiguous	0.5353	ambiguous	-0.128	Destabilizing	0.999	D	0.643	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.