TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26049	78370;78371;78372	chr2:178567987;178567986;178567985	chr2:179432714;179432713;179432712
N2AB	24408	73447;73448;73449	chr2:178567987;178567986;178567985	chr2:179432714;179432713;179432712
N2A	23481	70666;70667;70668	chr2:178567987;178567986;178567985	chr2:179432714;179432713;179432712
N2B	16984	51175;51176;51177	chr2:178567987;178567986;178567985	chr2:179432714;179432713;179432712
Novex-1	17109	51550;51551;51552	chr2:178567987;178567986;178567985	chr2:179432714;179432713;179432712
Novex-2	17176	51751;51752;51753	chr2:178567987;178567986;178567985	chr2:179432714;179432713;179432712
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: Fn3-77
• Domain position: 60
• Structural Position: 90
• Q(SASA): 0.5269
• 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	rs1706572074	None	0.003	N	0.151	0.082	0.168933306366	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
Q/K	rs1706572074	None	0.003	N	0.151	0.082	0.168933306366	gnomAD-4.0.0	6.57791E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.47102E-05	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	0.1682	likely_benign	0.1746	benign	-0.598	Destabilizing	0.028	N	0.317	neutral	None	None	None	None	N
Q/C	0.3178	likely_benign	0.2914	benign	-0.064	Destabilizing	0.942	D	0.455	neutral	None	None	None	None	N
Q/D	0.3928	ambiguous	0.3704	ambiguous	-0.351	Destabilizing	0.236	N	0.284	neutral	None	None	None	None	N
Q/E	0.094	likely_benign	0.0924	benign	-0.248	Destabilizing	0.092	N	0.277	neutral	N	0.3965366	None	None	N
Q/F	0.4239	ambiguous	0.4096	ambiguous	-0.25	Destabilizing	0.273	N	0.496	neutral	None	None	None	None	N
Q/G	0.2899	likely_benign	0.2902	benign	-0.953	Destabilizing	0.063	N	0.329	neutral	None	None	None	None	N
Q/H	0.1161	likely_benign	0.104	benign	-0.623	Destabilizing	0.002	N	0.185	neutral	N	0.442271676	None	None	N
Q/I	0.2052	likely_benign	0.2076	benign	0.306	Stabilizing	0.428	N	0.501	neutral	None	None	None	None	N
Q/K	0.0862	likely_benign	0.0849	benign	-0.315	Destabilizing	0.003	N	0.151	neutral	N	0.438172579	None	None	N
Q/L	0.1023	likely_benign	0.1043	benign	0.306	Stabilizing	0.048	N	0.326	neutral	N	0.520116385	None	None	N
Q/M	0.2268	likely_benign	0.2362	benign	0.553	Stabilizing	0.942	D	0.344	neutral	None	None	None	None	N
Q/N	0.2136	likely_benign	0.2038	benign	-0.9	Destabilizing	0.236	N	0.285	neutral	None	None	None	None	N
Q/P	0.6772	likely_pathogenic	0.6793	pathogenic	0.036	Stabilizing	0.534	D	0.373	neutral	N	0.513921131	None	None	N
Q/R	0.0838	likely_benign	0.0793	benign	-0.21	Destabilizing	None	N	0.127	neutral	N	0.418546668	None	None	N
Q/S	0.1695	likely_benign	0.1659	benign	-0.999	Destabilizing	0.004	N	0.124	neutral	None	None	None	None	N
Q/T	0.1147	likely_benign	0.1148	benign	-0.699	Destabilizing	0.004	N	0.201	neutral	None	None	None	None	N
Q/V	0.1347	likely_benign	0.1355	benign	0.036	Stabilizing	0.134	N	0.356	neutral	None	None	None	None	N
Q/W	0.4055	ambiguous	0.3683	ambiguous	-0.134	Destabilizing	0.842	D	0.467	neutral	None	None	None	None	N
Q/Y	0.2515	likely_benign	0.2318	benign	0.085	Stabilizing	0.001	N	0.203	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.