TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21094	63505;63506;63507	chr2:178588127;178588126;178588125	chr2:179452854;179452853;179452852
N2AB	19453	58582;58583;58584	chr2:178588127;178588126;178588125	chr2:179452854;179452853;179452852
N2A	18526	55801;55802;55803	chr2:178588127;178588126;178588125	chr2:179452854;179452853;179452852
N2B	12029	36310;36311;36312	chr2:178588127;178588126;178588125	chr2:179452854;179452853;179452852
Novex-1	12154	36685;36686;36687	chr2:178588127;178588126;178588125	chr2:179452854;179452853;179452852
Novex-2	12221	36886;36887;36888	chr2:178588127;178588126;178588125	chr2:179452854;179452853;179452852
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Fn3-41
• Domain position: 31
• Structural Position: 33
• Q(SASA): 0.2079
• 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
A/T	rs1408476291	None	0.716	N	0.692	0.184	0.354183961838	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
A/T	rs1408476291	None	0.716	N	0.692	0.184	0.354183961838	gnomAD-4.0.0	5.13148E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	9.58571E-06	0	0
A/V	None	None	0.834	N	0.741	0.277	0.459192005304	gnomAD-4.0.0	7.5313E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	9.89901E-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
A/C	0.5826	likely_pathogenic	0.4389	ambiguous	-0.747	Destabilizing	0.994	D	0.804	deleterious	None	None	None	None	I
A/D	0.8879	likely_pathogenic	0.8284	pathogenic	-0.891	Destabilizing	0.959	D	0.826	deleterious	None	None	None	None	I
A/E	0.8366	likely_pathogenic	0.7688	pathogenic	-1.033	Destabilizing	0.898	D	0.805	deleterious	N	0.465924281	None	None	I
A/F	0.6648	likely_pathogenic	0.5567	ambiguous	-1.07	Destabilizing	0.979	D	0.837	deleterious	None	None	None	None	I
A/G	0.2928	likely_benign	0.2116	benign	-0.667	Destabilizing	0.716	D	0.618	neutral	N	0.493905644	None	None	I
A/H	0.8006	likely_pathogenic	0.7291	pathogenic	-0.764	Destabilizing	0.994	D	0.825	deleterious	None	None	None	None	I
A/I	0.7673	likely_pathogenic	0.6427	pathogenic	-0.465	Destabilizing	0.959	D	0.817	deleterious	None	None	None	None	I
A/K	0.892	likely_pathogenic	0.8501	pathogenic	-0.946	Destabilizing	0.921	D	0.813	deleterious	None	None	None	None	I
A/L	0.4055	ambiguous	0.3139	benign	-0.465	Destabilizing	0.87	D	0.761	deleterious	None	None	None	None	I
A/M	0.5023	ambiguous	0.4008	ambiguous	-0.341	Destabilizing	0.998	D	0.816	deleterious	None	None	None	None	I
A/N	0.7509	likely_pathogenic	0.6439	pathogenic	-0.541	Destabilizing	0.921	D	0.823	deleterious	None	None	None	None	I
A/P	0.9859	likely_pathogenic	0.9771	pathogenic	-0.46	Destabilizing	0.946	D	0.818	deleterious	N	0.486309942	None	None	I
A/Q	0.7231	likely_pathogenic	0.6442	pathogenic	-0.853	Destabilizing	0.959	D	0.828	deleterious	None	None	None	None	I
A/R	0.8177	likely_pathogenic	0.7772	pathogenic	-0.427	Destabilizing	0.959	D	0.819	deleterious	None	None	None	None	I
A/S	0.1256	likely_benign	0.0984	benign	-0.742	Destabilizing	0.035	N	0.556	neutral	N	0.389109195	None	None	I
A/T	0.2805	likely_benign	0.2202	benign	-0.809	Destabilizing	0.716	D	0.692	prob.neutral	N	0.483118221	None	None	I
A/V	0.4843	ambiguous	0.3758	ambiguous	-0.46	Destabilizing	0.834	D	0.741	deleterious	N	0.469647264	None	None	I
A/W	0.9471	likely_pathogenic	0.913	pathogenic	-1.235	Destabilizing	0.998	D	0.825	deleterious	None	None	None	None	I
A/Y	0.8035	likely_pathogenic	0.7136	pathogenic	-0.895	Destabilizing	0.994	D	0.837	deleterious	None	None	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.