TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25062	75409;75410;75411	chr2:178570948;178570947;178570946	chr2:179435675;179435674;179435673
N2AB	23421	70486;70487;70488	chr2:178570948;178570947;178570946	chr2:179435675;179435674;179435673
N2A	22494	67705;67706;67707	chr2:178570948;178570947;178570946	chr2:179435675;179435674;179435673
N2B	15997	48214;48215;48216	chr2:178570948;178570947;178570946	chr2:179435675;179435674;179435673
Novex-1	16122	48589;48590;48591	chr2:178570948;178570947;178570946	chr2:179435675;179435674;179435673
Novex-2	16189	48790;48791;48792	chr2:178570948;178570947;178570946	chr2:179435675;179435674;179435673
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Fn3-70
• Domain position: 57
• Structural Position: 83
• Q(SASA): 0.8635
• 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
I/S	None	None	0.379	N	0.394	0.183	0.661538273795	gnomAD-4.0.0	6.84288E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99572E-07	0	0
I/T	rs1010492126	-0.354	0.016	N	0.233	0.143	0.453214075403	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
I/T	rs1010492126	-0.354	0.016	N	0.233	0.143	0.453214075403	gnomAD-4.0.0	2.05286E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99572E-07	2.31879E-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
I/A	0.1751	likely_benign	0.1899	benign	-0.574	Destabilizing	0.25	N	0.37	neutral	None	None	None	None	I
I/C	0.6813	likely_pathogenic	0.71	pathogenic	-0.683	Destabilizing	0.992	D	0.373	neutral	None	None	None	None	I
I/D	0.7127	likely_pathogenic	0.7493	pathogenic	0.053	Stabilizing	0.92	D	0.399	neutral	None	None	None	None	I
I/E	0.561	ambiguous	0.6072	pathogenic	-0.031	Destabilizing	0.92	D	0.385	neutral	None	None	None	None	I
I/F	0.2166	likely_benign	0.2216	benign	-0.545	Destabilizing	0.81	D	0.389	neutral	N	0.502010626	None	None	I
I/G	0.4972	ambiguous	0.5226	ambiguous	-0.735	Destabilizing	0.92	D	0.371	neutral	None	None	None	None	I
I/H	0.509	ambiguous	0.5413	ambiguous	0.017	Stabilizing	0.992	D	0.376	neutral	None	None	None	None	I
I/K	0.3794	ambiguous	0.4088	ambiguous	-0.272	Destabilizing	0.85	D	0.371	neutral	None	None	None	None	I
I/L	0.088	likely_benign	0.091	benign	-0.274	Destabilizing	0.002	N	0.105	neutral	N	0.431841252	None	None	I
I/M	0.0817	likely_benign	0.0876	benign	-0.395	Destabilizing	0.036	N	0.269	neutral	N	0.517094722	None	None	I
I/N	0.3038	likely_benign	0.3148	benign	-0.123	Destabilizing	0.896	D	0.405	neutral	N	0.449464221	None	None	I
I/P	0.3569	ambiguous	0.388	ambiguous	-0.341	Destabilizing	0.972	D	0.402	neutral	None	None	None	None	I
I/Q	0.384	ambiguous	0.4229	ambiguous	-0.315	Destabilizing	0.92	D	0.393	neutral	None	None	None	None	I
I/R	0.2857	likely_benign	0.3091	benign	0.245	Stabilizing	0.85	D	0.405	neutral	None	None	None	None	I
I/S	0.2211	likely_benign	0.2274	benign	-0.614	Destabilizing	0.379	N	0.394	neutral	N	0.439055226	None	None	I
I/T	0.1023	likely_benign	0.1034	benign	-0.585	Destabilizing	0.016	N	0.233	neutral	N	0.42687815	None	None	I
I/V	0.0924	likely_benign	0.095	benign	-0.341	Destabilizing	0.099	N	0.271	neutral	N	0.481192637	None	None	I
I/W	0.7227	likely_pathogenic	0.7531	pathogenic	-0.554	Destabilizing	0.992	D	0.427	neutral	None	None	None	None	I
I/Y	0.584	likely_pathogenic	0.608	pathogenic	-0.306	Destabilizing	0.92	D	0.396	neutral	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.