TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30315	91168;91169;91170	chr2:178551957;178551956;178551955	chr2:179416684;179416683;179416682
N2AB	28674	86245;86246;86247	chr2:178551957;178551956;178551955	chr2:179416684;179416683;179416682
N2A	27747	83464;83465;83466	chr2:178551957;178551956;178551955	chr2:179416684;179416683;179416682
N2B	21250	63973;63974;63975	chr2:178551957;178551956;178551955	chr2:179416684;179416683;179416682
Novex-1	21375	64348;64349;64350	chr2:178551957;178551956;178551955	chr2:179416684;179416683;179416682
Novex-2	21442	64549;64550;64551	chr2:178551957;178551956;178551955	chr2:179416684;179416683;179416682
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: Fn3-108
• Domain position: 92
• Structural Position: 126
• Q(SASA): 0.6295
• 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/T	rs755698637	-0.572	None	N	0.089	0.112	0.402614778071	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.88E-06	0
I/T	rs755698637	-0.572	None	N	0.089	0.112	0.402614778071	gnomAD-4.0.0	2.73899E-06	None	None	None	None	I	None	8.96647E-05	0	None	0	2.52143E-05	None	0	0	0	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
I/A	0.1218	likely_benign	0.1299	benign	-1.015	Destabilizing	0.002	N	0.165	neutral	None	None	None	None	I
I/C	0.3322	likely_benign	0.3874	ambiguous	-0.822	Destabilizing	0.131	N	0.289	neutral	None	None	None	None	I
I/D	0.2653	likely_benign	0.2681	benign	-0.119	Destabilizing	None	N	0.152	neutral	None	None	None	None	I
I/E	0.2655	likely_benign	0.2667	benign	-0.149	Destabilizing	None	N	0.166	neutral	None	None	None	None	I
I/F	0.1268	likely_benign	0.1643	benign	-0.656	Destabilizing	0.008	N	0.335	neutral	N	0.444048119	None	None	I
I/G	0.2922	likely_benign	0.3089	benign	-1.269	Destabilizing	0.009	N	0.411	neutral	None	None	None	None	I
I/H	0.2363	likely_benign	0.2728	benign	-0.348	Destabilizing	0.131	N	0.392	neutral	None	None	None	None	I
I/K	0.186	likely_benign	0.2097	benign	-0.554	Destabilizing	0.004	N	0.401	neutral	None	None	None	None	I
I/L	0.0834	likely_benign	0.0948	benign	-0.429	Destabilizing	None	N	0.096	neutral	N	0.395139451	None	None	I
I/M	0.0821	likely_benign	0.0917	benign	-0.5	Destabilizing	0.027	N	0.322	neutral	N	0.445088269	None	None	I
I/N	0.0971	likely_benign	0.0951	benign	-0.436	Destabilizing	0.008	N	0.505	neutral	N	0.393526085	None	None	I
I/P	0.2478	likely_benign	0.263	benign	-0.59	Destabilizing	0.041	N	0.551	neutral	None	None	None	None	I
I/Q	0.2159	likely_benign	0.2283	benign	-0.594	Destabilizing	0.01	N	0.535	neutral	None	None	None	None	I
I/R	0.1609	likely_benign	0.1919	benign	-0.011	Destabilizing	0.021	N	0.567	neutral	None	None	None	None	I
I/S	0.1122	likely_benign	0.1103	benign	-1.044	Destabilizing	0.003	N	0.251	neutral	N	0.37863399	None	None	I
I/T	0.0975	likely_benign	0.1076	benign	-0.952	Destabilizing	None	N	0.089	neutral	N	0.367070203	None	None	I
I/V	0.0544	likely_benign	0.0561	benign	-0.59	Destabilizing	None	N	0.075	neutral	N	0.41285842	None	None	I
I/W	0.6696	likely_pathogenic	0.7526	pathogenic	-0.663	Destabilizing	0.633	D	0.338	neutral	None	None	None	None	I
I/Y	0.326	likely_benign	0.3787	ambiguous	-0.43	Destabilizing	0.131	N	0.425	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.