TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6874	20845;20846;20847	chr2:178725584;178725583;178725582	chr2:179590311;179590310;179590309
N2AB	6557	19894;19895;19896	chr2:178725584;178725583;178725582	chr2:179590311;179590310;179590309
N2A	5630	17113;17114;17115	chr2:178725584;178725583;178725582	chr2:179590311;179590310;179590309
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: CAA
• RefSeq wild type template codon: GTT
• Domain: Ig-53
• Domain position: 21
• Structural Position: 31
• Q(SASA): 0.5738
• 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	None	None	0.996	N	0.539	0.242	0.29385284311	gnomAD-4.0.0	1.5949E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86372E-06	0	0
Q/R	rs749312103	0.333	0.959	N	0.445	0.191	0.257786959452	gnomAD-2.1.1	4.05E-06	None	None	None	None	N	None	0	0	None	0	5.58E-05	None	0	None	0	0	0
Q/R	rs749312103	0.333	0.959	N	0.445	0.191	0.257786959452	gnomAD-4.0.0	1.36994E-06	None	None	None	None	N	None	0	0	None	0	2.52105E-05	None	0	0	9.0009E-07	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	0.289	likely_benign	0.2886	benign	-0.558	Destabilizing	0.863	D	0.483	neutral	None	None	None	None	N
Q/C	0.6528	likely_pathogenic	0.599	pathogenic	0.015	Stabilizing	0.999	D	0.559	neutral	None	None	None	None	N
Q/D	0.6081	likely_pathogenic	0.6239	pathogenic	-0.498	Destabilizing	0.99	D	0.471	neutral	None	None	None	None	N
Q/E	0.1084	likely_benign	0.1103	benign	-0.444	Destabilizing	0.967	D	0.483	neutral	N	0.506774233	None	None	N
Q/F	0.6746	likely_pathogenic	0.6477	pathogenic	-0.396	Destabilizing	0.982	D	0.579	neutral	None	None	None	None	N
Q/G	0.3603	ambiguous	0.3718	ambiguous	-0.872	Destabilizing	0.969	D	0.541	neutral	None	None	None	None	N
Q/H	0.2351	likely_benign	0.2096	benign	-0.817	Destabilizing	0.996	D	0.539	neutral	N	0.484429017	None	None	N
Q/I	0.3733	ambiguous	0.3562	ambiguous	0.221	Stabilizing	0.759	D	0.525	neutral	None	None	None	None	N
Q/K	0.0778	likely_benign	0.079	benign	-0.248	Destabilizing	0.906	D	0.491	neutral	N	0.520743608	None	None	N
Q/L	0.1696	likely_benign	0.1648	benign	0.221	Stabilizing	0.005	N	0.376	neutral	D	0.529845881	None	None	N
Q/M	0.4152	ambiguous	0.3945	ambiguous	0.674	Stabilizing	0.373	N	0.309	neutral	None	None	None	None	N
Q/N	0.4411	ambiguous	0.4389	ambiguous	-0.712	Destabilizing	0.99	D	0.496	neutral	None	None	None	None	N
Q/P	0.4758	ambiguous	0.6549	pathogenic	-0.007	Destabilizing	0.996	D	0.587	neutral	N	0.508863148	None	None	N
Q/R	0.0876	likely_benign	0.0824	benign	-0.152	Destabilizing	0.959	D	0.445	neutral	N	0.489744934	None	None	N
Q/S	0.341	ambiguous	0.3426	ambiguous	-0.777	Destabilizing	0.969	D	0.471	neutral	None	None	None	None	N
Q/T	0.221	likely_benign	0.2151	benign	-0.536	Destabilizing	0.969	D	0.509	neutral	None	None	None	None	N
Q/V	0.2552	likely_benign	0.2465	benign	-0.007	Destabilizing	0.759	D	0.497	neutral	None	None	None	None	N
Q/W	0.5441	ambiguous	0.5005	ambiguous	-0.263	Destabilizing	0.999	D	0.566	neutral	None	None	None	None	N
Q/Y	0.4928	ambiguous	0.4558	ambiguous	-0.041	Destabilizing	0.997	D	0.589	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.