TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20664	62215;62216;62217	chr2:178589735;178589734;178589733	chr2:179454462;179454461;179454460
N2AB	19023	57292;57293;57294	chr2:178589735;178589734;178589733	chr2:179454462;179454461;179454460
N2A	18096	54511;54512;54513	chr2:178589735;178589734;178589733	chr2:179454462;179454461;179454460
N2B	11599	35020;35021;35022	chr2:178589735;178589734;178589733	chr2:179454462;179454461;179454460
Novex-1	11724	35395;35396;35397	chr2:178589735;178589734;178589733	chr2:179454462;179454461;179454460
Novex-2	11791	35596;35597;35598	chr2:178589735;178589734;178589733	chr2:179454462;179454461;179454460
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAC
• RefSeq wild type template codon: TTG
• Domain: Fn3-37
• Domain position: 96
• Structural Position: 132
• Q(SASA): 0.8918
• Predicted PPI site: I

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
N/D	rs879206414	None	0.005	N	0.129	0.139	None	gnomAD-4.0.0	2.02981E-06	None	None	None	None	I	None	3.48663E-05	0	None	0	0	None	0	0	0	0	0
N/I	rs1214786970	0.32	0.996	N	0.701	0.418	0.490074841992	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
N/I	rs1214786970	0.32	0.996	N	0.701	0.418	0.490074841992	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	0	6.55E-05	0	0	0	None	0	0	0	0	0
N/I	rs1214786970	0.32	0.996	N	0.701	0.418	0.490074841992	gnomAD-4.0.0	3.84458E-06	None	None	None	None	I	None	0	3.39006E-05	None	0	0	None	0	0	2.39399E-06	0	0
N/K	rs376455983	0.53	0.919	N	0.52	0.183	0.173771789658	gnomAD-2.1.1	2.86E-05	None	None	None	None	I	None	4.13E-05	0	None	0	0	None	0	None	0	5.48E-05	0
N/K	rs376455983	0.53	0.919	N	0.52	0.183	0.173771789658	gnomAD-3.1.2	5.26E-05	None	None	None	None	I	None	2.41E-05	0	0	0	0	None	0	0	1.02968E-04	0	0
N/K	rs376455983	0.53	0.919	N	0.52	0.183	0.173771789658	gnomAD-4.0.0	2.7372E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.69874E-06	1.15947E-05	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
N/A	0.5518	ambiguous	0.4485	ambiguous	-0.208	Destabilizing	0.968	D	0.521	neutral	None	None	None	None	I
N/C	0.6296	likely_pathogenic	0.5483	ambiguous	0.293	Stabilizing	0.999	D	0.755	deleterious	None	None	None	None	I
N/D	0.1627	likely_benign	0.136	benign	0.166	Stabilizing	0.005	N	0.129	neutral	N	0.354071115	None	None	I
N/E	0.7198	likely_pathogenic	0.589	pathogenic	0.123	Stabilizing	0.757	D	0.523	neutral	None	None	None	None	I
N/F	0.8517	likely_pathogenic	0.7746	pathogenic	-0.651	Destabilizing	0.997	D	0.661	prob.neutral	None	None	None	None	I
N/G	0.7008	likely_pathogenic	0.6367	pathogenic	-0.359	Destabilizing	0.862	D	0.521	neutral	None	None	None	None	I
N/H	0.237	likely_benign	0.2122	benign	-0.396	Destabilizing	0.996	D	0.513	neutral	N	0.475898674	None	None	I
N/I	0.6616	likely_pathogenic	0.458	ambiguous	0.095	Stabilizing	0.996	D	0.701	prob.delet.	N	0.468759271	None	None	I
N/K	0.8556	likely_pathogenic	0.7127	pathogenic	0.106	Stabilizing	0.919	D	0.52	neutral	N	0.469452704	None	None	I
N/L	0.5617	ambiguous	0.4283	ambiguous	0.095	Stabilizing	0.991	D	0.621	neutral	None	None	None	None	I
N/M	0.7297	likely_pathogenic	0.624	pathogenic	0.277	Stabilizing	0.999	D	0.668	prob.neutral	None	None	None	None	I
N/P	0.8633	likely_pathogenic	0.7717	pathogenic	0.02	Stabilizing	0.997	D	0.681	prob.neutral	None	None	None	None	I
N/Q	0.693	likely_pathogenic	0.5954	pathogenic	-0.307	Destabilizing	0.991	D	0.559	neutral	None	None	None	None	I
N/R	0.8534	likely_pathogenic	0.7412	pathogenic	0.14	Stabilizing	0.991	D	0.561	neutral	None	None	None	None	I
N/S	0.1215	likely_benign	0.1095	benign	-0.083	Destabilizing	0.824	D	0.597	neutral	N	0.44084195	None	None	I
N/T	0.3234	likely_benign	0.2479	benign	0.009	Stabilizing	0.958	D	0.486	neutral	N	0.428640657	None	None	I
N/V	0.6511	likely_pathogenic	0.4933	ambiguous	0.02	Stabilizing	0.997	D	0.685	prob.delet.	None	None	None	None	I
N/W	0.9329	likely_pathogenic	0.9136	pathogenic	-0.699	Destabilizing	0.999	D	0.81	deleterious	None	None	None	None	I
N/Y	0.421	ambiguous	0.3222	benign	-0.408	Destabilizing	0.996	D	0.661	prob.neutral	N	0.46073722	None	None	I

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.