TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25498	76717;76718;76719	chr2:178569640;178569639;178569638	chr2:179434367;179434366;179434365
N2AB	23857	71794;71795;71796	chr2:178569640;178569639;178569638	chr2:179434367;179434366;179434365
N2A	22930	69013;69014;69015	chr2:178569640;178569639;178569638	chr2:179434367;179434366;179434365
N2B	16433	49522;49523;49524	chr2:178569640;178569639;178569638	chr2:179434367;179434366;179434365
Novex-1	16558	49897;49898;49899	chr2:178569640;178569639;178569638	chr2:179434367;179434366;179434365
Novex-2	16625	50098;50099;50100	chr2:178569640;178569639;178569638	chr2:179434367;179434366;179434365
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Fn3-73
• Domain position: 94
• Structural Position: 126
• Q(SASA): 0.5348
• 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
P/A	rs377754701	-0.486	0.07	N	0.265	0.087	0.223146558224	gnomAD-2.1.1	8.6E-05	None	None	None	None	N	None	0	0	None	0	0	None	6.92886E-04	None	0	0	0
P/A	rs377754701	-0.486	0.07	N	0.265	0.087	0.223146558224	gnomAD-3.1.2	3.29E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	0	1.03648E-03	0
P/A	rs377754701	-0.486	0.07	N	0.265	0.087	0.223146558224	1000 genomes	5.99042E-04	None	None	None	None	N	None	0	0	None	None	0	0	None	None	None	3.1E-03	None
P/A	rs377754701	-0.486	0.07	N	0.265	0.087	0.223146558224	gnomAD-4.0.0	5.83184E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	9.79292E-04	8.01436E-05
P/H	rs374426354	None	0.947	N	0.517	0.281	0.432266382184	gnomAD-4.0.0	1.37006E-06	None	None	None	None	N	None	5.98265E-05	0	None	0	0	None	0	0	0	0	0
P/L	rs374426354	-0.133	0.146	N	0.299	0.199	None	gnomAD-2.1.1	8.18E-06	None	None	None	None	N	None	0	2.93E-05	None	0	0	None	0	None	0	9.07E-06	0
P/L	rs374426354	-0.133	0.146	N	0.299	0.199	None	gnomAD-3.1.2	1.32E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	2.94E-05	0	0
P/L	rs374426354	-0.133	0.146	N	0.299	0.199	None	gnomAD-4.0.0	1.42696E-05	None	None	None	None	N	None	0	1.67499E-05	None	0	0	None	0	0	1.86598E-05	0	0
P/S	rs377754701	-0.648	0.002	N	0.177	0.078	None	gnomAD-2.1.1	4.09E-06	None	None	None	None	N	None	6.59E-05	0	None	0	0	None	0	None	0	0	0
P/S	rs377754701	-0.648	0.002	N	0.177	0.078	None	gnomAD-3.1.2	1.32E-05	None	None	None	None	N	None	4.83E-05	0	0	0	0	None	0	0	0	0	0
P/S	rs377754701	-0.648	0.002	N	0.177	0.078	None	gnomAD-4.0.0	1.86136E-06	None	None	None	None	N	None	4.01016E-05	0	None	0	0	None	0	0	0	0	0
P/T	None	None	0.005	N	0.213	0.076	0.230578612272	gnomAD-4.0.0	7.53565E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.90122E-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
P/A	0.0641	likely_benign	0.0621	benign	-0.767	Destabilizing	0.07	N	0.265	neutral	N	0.50882945	None	None	N
P/C	0.2568	likely_benign	0.2415	benign	-0.716	Destabilizing	0.96	D	0.501	neutral	None	None	None	None	N
P/D	0.3495	ambiguous	0.2978	benign	-0.418	Destabilizing	0.312	N	0.397	neutral	None	None	None	None	N
P/E	0.2233	likely_benign	0.1976	benign	-0.504	Destabilizing	0.312	N	0.346	neutral	None	None	None	None	N
P/F	0.334	likely_benign	0.3098	benign	-0.774	Destabilizing	0.794	D	0.649	prob.neutral	None	None	None	None	N
P/G	0.2133	likely_benign	0.1888	benign	-0.958	Destabilizing	0.185	N	0.317	neutral	None	None	None	None	N
P/H	0.1287	likely_benign	0.114	benign	-0.42	Destabilizing	0.947	D	0.517	neutral	N	0.485597201	None	None	N
P/I	0.2012	likely_benign	0.1843	benign	-0.398	Destabilizing	0.355	N	0.565	neutral	None	None	None	None	N
P/K	0.1387	likely_benign	0.1285	benign	-0.664	Destabilizing	0.002	N	0.179	neutral	None	None	None	None	N
P/L	0.1081	likely_benign	0.1027	benign	-0.398	Destabilizing	0.146	N	0.299	neutral	N	0.46069209	None	None	N
P/M	0.2109	likely_benign	0.1936	benign	-0.397	Destabilizing	0.041	N	0.319	neutral	None	None	None	None	N
P/N	0.1779	likely_benign	0.1512	benign	-0.402	Destabilizing	0.524	D	0.474	neutral	None	None	None	None	N
P/Q	0.1112	likely_benign	0.103	benign	-0.635	Destabilizing	0.524	D	0.499	neutral	None	None	None	None	N
P/R	0.116	likely_benign	0.1072	benign	-0.105	Destabilizing	0.294	N	0.472	neutral	N	0.473480427	None	None	N
P/S	0.0924	likely_benign	0.0853	benign	-0.836	Destabilizing	0.002	N	0.177	neutral	N	0.449282502	None	None	N
P/T	0.0761	likely_benign	0.0688	benign	-0.815	Destabilizing	0.005	N	0.213	neutral	N	0.445548763	None	None	N
P/V	0.1482	likely_benign	0.1362	benign	-0.484	Destabilizing	0.185	N	0.348	neutral	None	None	None	None	N
P/W	0.5695	likely_pathogenic	0.5135	ambiguous	-0.851	Destabilizing	0.989	D	0.527	neutral	None	None	None	None	N
P/Y	0.3154	likely_benign	0.2834	benign	-0.569	Destabilizing	0.96	D	0.606	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.